e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7

Official Journal of the European Paediatric Neurology Society

Original article

Neonatal hypoglycemia: A wide range of

electroclinical manifestations and seizure
outcomes
€
Ebru Arhan, Zeynep Oztürk *
lu, Kürs‚ad Aydın,
, Ays‚e Serdarog
ba Hirfanog
Tug lu, Yılmaz Akbas‚
Gazi University, Faculty of Medicine, Department of Pediatric Neurology, Turkey

article info abstract

Article history: Purpose: We examined the various types of epilepsy in children with neonatal hypoglyce-
Received 9 July 2016 mia in order to define electroclinical and prognostic features of these patients.
Received in revised form Method: We retrospectively reviewed the medical records of patients with a history of
21 March 2017 symptomatic neonatal hypoglycaemia who have been followed at Gazi University Hospital
Accepted 24 May 2017 Pediatric Neurology Department between 2006 and 2015. Patients with perinatal asphyxia
were excluded. Details of each patient's perinatal history, neurological outcome, epilepsy
Keywords: details, seizure outcome and EEG and brain MRI findings were reviewed.
Neonatal hypoglycemia Results: Fourty five patients (range 6 moe15 y) with a history of symptomatic neonatal
Electroclinical hypoglycaemia were included the study. Epilepsy developed in 36 patients and 23 of them
Outcome had intractable epilepsy. All patients had occipital brain injury.
Intractable epilepsy Conclusion: We observed that most of the patients, either manifesting focal or generalized
Glucose seizures, further develop intractable epilepsy. This finding establishes neonatal hypogly-
cemia as a possible cause to be considered in any case of intractable epilepsy.
© 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights
reserved.

epilepsy. The frequency of epilepsy after symptomatic

1. Introduction neonatal hypoglycaemia is greater than 50%.5e7 However, the
spectrum of hypoglycemic brain injury resulting in epilepsy is
Glucose is the primary energy source of the human brain, unclear. Most of existing literature on this topic is focused on
therefore highly susceptible to hypoglycemic damage with a the incidence of seizures in large cohorts of epileptic patients
high risk of neurologic handicap including; cerebral palsy, after neonatal hypoglycemia with only a few studies
intellectual disability, blindness and epilepsy.1e4 Hypoglyce- describing the clinical, EEG, and syndromic aspects specif-
mic brain injury is a recognized insult that triggers seizures ically.5,7,8 To add to the knowledge base of this subject, in the
and is typically associated with both focal and generalized

* Corresponding author. Gazi University, Faculty of Medicine, Department of Pediatric Neurology, Besevler, Ankara 06510, Turkey. Fax:
þ90 312 21501 43.
€
E-mail address: [email protected] (Z. Oztürk).
http://dx.doi.org/10.1016/j.ejpn.2017.05.009
1090-3798/© 2017 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009
2 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7

present study, we examined the various types of epilepsy in was accepted as the first seizure after the neonatal period. The
children with neonatal hyperglycemia in order to define epileptic syndromes were analyzed in detail. EEG of each pa-
electroclinical and prognostic features of these patients. This tient was reviewed with respect to background abnormality
information will enable earlier identification of patients, (slowing of the background EEG rhythm, intermittent or
thereby preventing the progression. To our knowledge, this continuous generalized, localized or regional slowing), the
study is the largest report on a detailed analysis of the spec- localization (generalized, focal, multifocal), morphology spike,
trum of epilepsy in neonatal hypoglycemia. polyspike, sharp wave, spike wave, sharp slow wave, and
polyspike wave, and topography of interictal epileptiform
discharges (IEDs). The classification of seizures was based on
2. Material method the clinical and EEG findings according to the criteria of In-
ternational League Against Epilepsy.11 In all cases, cranial MRI
A retrospective electronic chart review using the key words was performed with epilepsy protocol using superconducting
“neonatal hypoglycemia”, “epilepsy” was performed to iden- magnets with multichannel head coils in the supine position
tify patients who had a neurological handicap after neonatal with a 1.5 T MRI (GE SIGNA EXCITE, Milwaukee, USA). Epilepsy
hypoglycemia and subsequently followed at Gazi University protocol included axial and sagittal T1 weighted, axial T2
Hospital Pediatric Neurology Department between 2006 and weighted, oblique coronal FLAIR perpendicular to the long
2015. Gazi University Hospital Pediatric Neurology Depart- axis of both hippocampi, and 3D inversion recovery (IR). The
ment provides primary to tertiary levels of care for children whole brain volumetric series were acquired using a 3D IR
with neurological disorders. The routine and video-EEG labo- technique with a slice of 1 mm thickness, zero interslice gap,
ratories perform about 1500 pediatric EEGs per year. A total of 256  222 matrix size, and a single signal average. T2 weighted
892 patients' charts were reviewed and, of these, 45 patients oblique axial images through the long axis of both hippocampi
were found who were followed with neurological disorders consisting of 20 slices were also obtained with 3 mm slice
after neonatal hypoglycemia. Of these, 36 patients were fol- thickness and 0.75 mm interslice gap. All MRI slices were re-
lowed with epilepsy after neonatal hypoglycemia. These 36 evaluated by K.A., who is most experienced and educated
subjects form the basis of the current report. Patients with a physician in MRI interpretation in the group.
history of perinatal asphyxia and patients without docu- Statistic analysis was performed with the SPSS statistical
mented hypoglycemia and apgar score at 5 min after delivery analysis program using the x2 test. P values of less than 0.05
less than 7 were excluded from the study. Hypoglycemia, was were regarded statistically significant.
defined as a whole blood glucose concentration of less than
47 mg per deciliter (2.6 mmol per liter). The study was
approved by the hospital's ethics committee. A total of 36 3. Results
subjects (26 male, 10 female, 11 moe18 y 5 mo; mean age 10 y
5 mo, at the time of review) who developed epilepsy after 3.1. Clinical manifestations
neonatal hypoglycemia were identified. Multiple clinical var-
iables in these 36 subjects were reviewed: neonatal hypogly- Twenty-nine patients were delivered at term, and seven pa-
cemia details, perinatal history, epilepsy details, imaging tients were delivered prematurely. One infant was the product
characteristics and neurological outcome. Neonatal hypogly- of twin pregnancy. All patients had Apgar scores >8 at 5 min.
cemia was classified by using a classification based on the One patient had a history of exposure to valproate during the
clinical setting, the presence of symptoms, the duration and first three months of pregnancy. At presentation, all patients
severity of hypoglycemia.9,10 According to this classification, had signs and symptoms of acute neurological dysfunction
patients were divided into two groups1; Early transitional associated with neonatal hypoglycaemia, with neonatal con-
neonatal hypoglycemia: typically occurring in the first 6e12 h vulsions evident in 20 (18 of them in the first 72 h of life), apnea
after sudden withdrawal of maternally derived substrate at in 3 and irritability in 3. Ten patients had prenatal and peri-
birth and resolved within 5 days or2 severe persistent neonatal natal problems (maternal diabetes (n:2), preeclampsia (n:4),
hypoglycaemia, caused by specific primary enzymatic or prematurity (n:7)) that made them prone to hypoglycemia
metabolic-endocrine abnormalities involving glucose ho- and/or medical problems other than hypoglycemia. Three
meostasis. Neonatal hypoglycemia details included; risk fac- patients were small for gestational age with birth weights of
tors (maternal conditions like gestational diabetes, 2000e2250 g, delivered at term. Three patients had indirect
preeclampsia, eclampsia), neonatal conditions (gestational hyperbilirubinemia requiring phototherapy; one patient had
age, gestational weight, sepsis, hyperbilirubinemia, intra- partial exchange transfusion for polycythemia. Neonatal
uterine growth retardation), duration of hypoglycemia. Etio- sepsis was diagnosed in three patients with a positive blood
logical investigation of neonatal hypoglycemia was performed culture in all. All infants had routine blood investigations
by laboratory tests including; amino acid profile, thyroid performed for neonatal hypoglycaemia. Transient neonatal
hormones (T4/TSH), growth hormone, insulin, cortisol and hypoglycaemia was diagnosed in 33 children, all of them had
acylcarnitines, and urine organic acids, ketone bodies. Hypo- feeding difficulty. Persistent neonatal hypoglycemia was
glycemia symptoms including seizures, poor feeding, hypo- diagnosed in three children, two of them had hyperinsulinism
thermia, apnea, altered consciousness, hypotonia were noted. and the other patient in the persistent group had pan-
Seizure onset, semiologic features, frequency, distribution, hypopituitarism. The minimum blood glucose ranged be-
duration of the seizures, drug treatment, seizure outcome tween 5 and 38 mg/dl (mean ± SD, 21.63 ± 1.33 mg/dl).
were analyzed from the medical records. Onset of epilepsy Duration of neonatal hypoglycemia ranged from 6 h to 3 days

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009
 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7 3

in the transient group whereas 2 days to 19 days in the 3.6. Clinical outcome and long term epilepsy evolution
persistent group.
At follow-up, 19 patients (52.7%) developed focal epilepsy with
3.2. EEG findings occipital features. Thirteen patients (36.1%) were progres-
sively controlled with AEDs and became seizure free. On the
Interictal EEG showed posterior temporooccipital (23 cases), other hand, six of these cases (19.4%) continued with daily to
multifocal or generalized spikes, polyspikes, and spike/wave weekly seizures with a combination of generalized tonic,
discharges (10 cases). Three patients had a normal initial EEG, myoclonic, and atonic seizures. Discontinuation of antiepi-
and eight showed an hypsarrhythmic EEG associated with leptic drugs (AEDs) was carried out in three patients who
infantile spasms at seizure onset. Interictal EEG remained became seizure-free during this follow-up period. Twenty-
abnormal in 32 of 36 patients (88.8%). For the 23 patients that three (63.8%) patients have evolved intractable epilepsy and
developed intractable seizures, interictal EEG remained presented with multiple seizure types. They included gener-
abnormal in all cases and showed persistent multifocal or alized epilepsy with tonic and toniceclonic seizures in 9 cases,
diffuse high-amplitude spikes mixed with irregular slow myoclonic seizures in 3, complex partial seizures in 4, atonic
waves (Fig. 1a,b,c). 8/23 (34.7%) previously presented epileptic seizures in 4, and epileptic spasm in 3 patients. 8/23 (34.7%)
encephalopathy with infantile spasms and evolved to Len- previously presented epileptic encephalopathy with infantile
noxeGastaut syndrome. For the 13 seizure-free patients, EEG spasms and evolved to LennoxeGastaut syndrome. Either due
was either normal6 or showed normal background activity to hyperinsulinism or panhypopituitarism, all three patients
with focal occipital spikes in two cases and temporal spikes in with persistent hypoglycemia, presented with infantile
one case. spasms and developmental delay, all had hypsarrhythmia on
EEG consistent with West syndrome and later evolved to
3.3. First seizures intractable epilepsy. Because of small number, we could not
make a statistical analysis for the risk factors.
The age at onset of seizures ranged from 2 to 144 months At follow-up, two patients have attention deficit hyperac-
(mean age, 18 months). Seizures started during the first 1 year tivity disorder, two autism, three mild intellectual disability,
of life in 26 patients (72%), at the median age of months. one severe intellectual disability and one moderate intellec-
Neonatal seizures were reported in twenty patients, in the tual disability. Three children with epilepsy also had cortical
remaining six patients, seizures started within age 6 months visual impairment and five had intellectual disability and two
and 12 months. Ten patients had onset of seizures after the had cerebral palsy.
age of one. First seizures were described as focal in 15 cases, When we evaluated the risk factors, severity, duration or
spasm in 12, secondary generalized focal seizures in 2 pa- the presence of neonatal seizures were not found related with
tients, myoclonic/clonic in 3, generalized in 3 and tonic in 1. long term seizure outcome, in the transient group (p: 0.673,
0.324, 0.89).
3.4. Neuroradiological findings

Brain magnetic resonance imaging (MRI) was performed in all

4. Discussion
patients with epilepsy at the median age of 1.5 years (range 6
monthse7 years). All patients had gliosis in the occipital white
Epilepsy is one of the main sequleas of neonatal hypoglycemia
matter bilaterally, with occipital cortical atrophy in 28 (Fig. 2).
but the prevalence of epilepsy following neonatal hypo-
Twenty two patients had additional gliosis in the parietal
glycaemia is unknown, and predictors of the clinical course
white matter (Fig. 3), with parietal cortical atrophy in four. One
yet remains unclear. Clinical and electrophysiological fea-
patient had pulvinar scarring (Fig. 3).
tures of epilepsy after neonatal hypoglycemia have been
analyzed, in only a few retrospective studies with limited
3.5. Treatments
number of patients.5,7,8 To the best of our knowledge, this is
the largest study assessing the electroclinical features of epi-
Initially, patients were treated with carbamazepine or val-
lepsy after isolated neonatal hypoglycemia and provides
proate in monotherapy, later, because of a worsening of sei-
insight into the wide range of electroclinical variabilities in
zures, antiepileptic polytherapy with a combination of
this group of patients. All patients in our series had occipital
different drugs (including phenobarbitale, valproate, carba-
brain injury which mainly seems to be the suspectible cause
mazepine, clobazam, leviteracetam, topiramate and vigaba-
of their epilepsy with a remarkable number of patients
trin) was introduced.
developing intractable epilepsy, which were not observed in
Strikingly, four patients (17.3%) developed encephalopathy
the previously reported series. Seizure outcome was favorable
with epileptic encephalopathy with continuous spike and
in most of the children with occipital epilepsy, but in neither
wave during sleep and treated with intravenous methy-
of the children with intractable epilepsy. The clinical signs of
prednisolone and clobasam. Vagus nerve stimulator was
neonatal hypoglycemia are variable and the level of blood
implanted in two of the intractable patients. Persistent
glucose concentration causing neonatal cerebral injury and
neonatal hypoglycemia was diagnosed in three children, two
leading to an acute neurological dysfunction is unclear.
of them had hyperinsulinism and eventually started on
Therefore, the definition of hypoglycemia is still controver-
diazoxide following glucose infusions and steroid treatment
sial.6,7,9,10 Current guidelines report that neonates presenting
and one of these patients had pancreatectomy at follow-up.

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009
4 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009
 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7 5

Fig. 2 e Coronal FLAIR and axial T2 imagings represent cortical atrophy and gliosis in the occipital lobes.

with acute neurological dysfunction and a blood glucose level variable range of electrophysiological outcome ranging from
of 1e2 mmol/L warrant treatment of the neonatal hypo- benign occipital epilepsy to intractable epilepsy in children
glycaemia.12 Our findings showing all of the patients pre- with isolated neonatal hypoglycemia. Although usually have
senting with acute neurologic, corroborate this consensus. a favorable outcome in previous studies, exceptionally it
Neonatal hypoglycemia may cause a well-defined pattern may diverge to intractable epilepsy and epileptic encepha-
of brain injury with a tendency for the involvement of parietal lopathy with continuous spike and wave during sleep, as
and occipital white matter, as seen in all our patients.13e16 The seen in our group. Patients in our series had isolated hypo-
reason for the involvement of parietal and occipital lobes is glycemia in the neonatal period, 23 out 36 had intractable
not exactly known.17e19 Excitatory neurotoxins active at N- epilepsy and four developed epileptic encephalopathy with
methyl-D-aspartate receptors, increased mitochondrial free continuous spike and wave during sleep. Occipital lobe
radical production, initiation of apoptosis and alterations in injury alone does not typically cause continuous spike and
cerebral energy production are the possible mechanisms of wave discharges whereas damage to the neighboring cortex
hypoglycemia induced cellular injury.20e23 It has been shown can be the real cause.12,14,26 The reason why some of these
that during hypoglycemia regional glucose uptake of occipital patients have intractable seizures is not known. Infantile
lobes decreases due to the increased regional cerebral blood spasms, generalized seizures, focal seizures, and febrile
flow24 A difference in regional blood flow may help hypogly- seizures have been previously reported in these patients.2 In
cemic damage through either loss of autoregulation or our study, eight patients had infantile spasms. Abnormal
delayed hypoperfusion. Neuronal injury in hypoglycemia may discharges in the occipital lobe are thought to activate
be limited to the areas with well-developed excitatory amino thalamus and reticular system causing infantile spasms.26,27
acid receptors.15 The differences in outcome of our patients may reflect the
The neuronal injury in hypoglycemia develop epilepsy, higher proportion of children with infantile spasms and the
mostly with a favorable prognosis and has been analyzed in severity or duration of neonatal hypoglycemia. Referral bias
previous papers. Recently, Fong et al. reported a benign to our tertiary center specializing in epilepsy may also
outcome in 9 out of 11 patients with focal seizures in line contribute to the capture of more unusual clinical pre-
with Caraballo and Montassir's reports.5,7,8 In contrast to sentations of this condition.
these, studies from Turkey and India reported intractable The seizure semiology and electrophysiological findings
seizures in 12 out of 23 and five out of 12 children, respec- with stereotyped occipital interictal discharges with sleep
tively.6,25 However, in these two studies patients had addi- activation, and a favorable outcome in thirteen patients are
tional neonatal co-morbidities. Our study demonstrates a suggestive of early-onset form of benign occipital epilepsy.

Fig. 1 e a: EEG recorded at the age of seven showing sharp waves in the right parietooccipital region. b: Sleep EEG recorded at
the age of nine showing electrical status epilepticus during sleep. c: Sleep EEG recorded at the age of three months showing
hypsarrhythmia.

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009
6 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7

Fig. 3 e Axial T2 imagings: Gliosis in the bilateral parietal and occipital white matter with cortical atrophy.

Benign focal epilepsies, both occipital and centrotemporal retrospective nature is the restrictive factor in our study.
spikes, are common in children with a variety of static brain Because we did not have any knowledge regarding the time
lesions and developmental disabilities.28e30 These benign that passed before the patient applied to our clinic, no
focal epilepsies reflect an age related maturational instability comment could be made on this issue. Further studies are
phenomena and the relationship to the underlying neuro- needed for defining the reason why some patients have a
developmental disorder or lesion may be coincidental. It is intractable epilepsy and to develop a protocol for the pre-
important to make a syndromic conceptualization because of vention of permanent brain damage due to hypoglycemia.
the age-limited nature.
Our data also emphasizes the importance of recognizing
inadequate feeding in the first days of life as a potential cause 5. Conclusion
of hypoglycemia. Transient neonatal hypoglycaemia due to
inadequate feeding was diagnosed in thirty three children in To our knowledge, we present the largest group of epileptic
our series. Because it may have devastating consequences patients with a single neonatal insult. This study establishes a
such as intractable epilepsy and is a preventable state of hy- wide range of electroclinical manifestation and seizure
poglycemia, it should be managed properly to avoid adverse outcome may evolve as a consequence of neonatal hypogly-
outcomes. As a persistent cause in neonatal hypoglycemia, an cemia and can range from benign occipital lobe seizures to
early and rapid diagnosis of hyperinsulinemic hypoglycemia epileptic encephalopathy with continuous spike and wave
is essential for preventing brain damage. Two patients with during sleep and intractable epilepsy. In our study, we
hyperinsulinemic hypoglycemia in our series had infantile observed that most of the patients, either manifesting focal or
spasm, hypsarthymia on EEG and evolved to intractable epi- generalized seizures, further develop intractable epilepsy.
lepsy at follow-up. Studies regarding seizure outcome in This finding establishes neonatal hypoglycemia as a possible
hyperinsulinemic hypoglycemia are lacking. Similar to our cause to be considered in any case of intractable epilepsy.
patients, recently Fong et al. reported five patients with Magnetic resonance imaging studies are essential to define
hyperinsulinemic hypoglycemia who presented with infantile the characteristics of cerebral lesions secondary to neonatal
spasm and have ongoing seizures despite treatment and hypoglycemia and to distinguish from other neonatal insults.
reminded hyperinsulinaemic hypoglycaemia as a cause of
persistent and recurrent neonatal hypoglycaemia.8 Our series
has several advantages over previous studies, such as large Conflict of interest
number, a homogenous group of isolated neonatal insult, and
long follow-up term covering electroclinical aspects. Our re- The authors have indicated they have no potential conflicts of
sults are quite different from previous studies.5,8 The interest to disclose.

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009
 e u r o p e a n j o u r n a l o f p a e d i a t r i c n e u r o l o g y x x x ( 2 0 1 7 ) 1 e7 7

references 16. Banker BQ. The neuropathological effects of anoxia and

hypoglycemia in the newborn. Dev Med Child Neurol
1967;9(5):544e50.
17. Filan PM, Inder TE, Cameron FJ, Kean MJ, Hunt RW. Neonatal
1. Cornblath M, Reisner SH. Blood glucose in the neonate and its
hypoglycemia and occipital cerebral injury. J Pediatr
clinical significance. N Engl J Med 1965;273(7):378e81.
2006;148(4):552e5.
2. Burns CM, Rutherford MA, Boardman JP, Cowan FM. Patterns
18. Kinnala A, Rikalainen H, Lapinleimu H, Parkkola R,
of cerebral injury and neurodevelopmental outcomes after
Kormano M, Kero P. Cerebral magnetic resonance imaging
symptomatic neonatal hypoglycemia. Pediatrics
and ultrasonography findings after neonatal hypoglycemia.
2008;122(1):65e74.
Pediatrics 1999;103(4 Pt 1):724e9.
3. Vannucci RC, Vannucci SJ. Hypoglycemic brain injury. Semin
19. Koh TH, Aynsley-Green A, Tarbit M, Eyre JA. Neural
Neonatol 2001;6(2):147e55.
dysfunction during hypoglycaemia. Arch Dis Child
4. Adamkin DH. Neonatal hypoglycemia. Curr Opin Pediatr
1988;63(11):1353e8.
2016;28(2):150e5.
20. Papagapiou MP, Auer RN. Regional neuroprotective effects of
5. Caraballo RH, Sakr D, Mozzi M, Guerrero A, Adi JN,
the NMDA receptor antagonist MK-801 (dizocilpine) in
Cersosimo RO, et al. Symptomatic occipital lobe epilepsy
hypoglycemic brain damage. J Cereb Blood Flow Metab
following neonatal hypoglycemia. Pediatr Neurol
1990;10(2):270e6.
2004;31(1):24e9.
21. Wieloch T. Hypoglycemia-induced neuronal damage
6. Udani V, Munot P, Ursekar M, Gupta S. Neonatal
prevented by an N-methyl-D-aspartate antagonist. Science
hypoglycemic brain e injury a common cause of infantile
1985;230(4726):681e3.
onset remote symptomatic epilepsy. Indian Pediatr
22. Ballesteros JR, Mishra OP, McGowan JE. Alterations in cerebral
2009;46(2):127e32.
mitochondria during acute hypoglycemia. Biol Neonate
7. Montassir H, Maegaki Y, Ohno K, Ogura K. Long term
2003;84(2):159e63.
prognosis of symptomatic occipital lobe epilepsy secondary
23. Imai T, Kondo M, Isobe K, Itoh S, Onishi S. Cerebral energy
to neonatal hypoglycemia. Epilepsy Res 2010;88(2e3):93e9.
metabolism in insulin induced hypoglycemia in newborn
8. Fong CY, Harvey AS. Variable outcome for epilepsy after
piglets: in vivo 31P-nuclear magnetic resonance spectroscopy.
neonatal hypoglycaemia. Dev Med Child Neurol
Acta Paediatr Jpn 1996;38(4):343e7.
2014;56(11):1093e9.
24. Mujsce DJ, Christensen MA, Vannucci RC. Regional cerebral
9. LaFranchi S. Hypoglycemia of infancy and childhood. Pediatr
blood flow and glucose utilization during hypoglycemia in
Clin North Am 1987;34(4):961e82.
newborn dogs. Am J Physiol 1989;256(6 Pt 2):H1659e66.
10. Sperling MA, Menon RK. Differential diagnosis and
25. Yalnizoglu D, Haliloglu G, Turanli G, Cila A, Topcu M. Neurologic
management of neonatal hypoglycemia. Pediatr Clin North Am
outcome in patients with MRI pattern of damage typical for
2004;51(3):703e23. x.
neonatal hypoglycemia. Brain Dev 2007;29(5):285e92.
11. Blume WT, Luders HO, Mizrahi E, Tassinari C, van Emde
26. Wang SM, Yang CS, Hou Y, Ma XW, Feng ZC, Liao YZ.
Boas W, Engel Jr J. Glossary of descriptive terminology for ictal
Perinatal occipital lobe injury in children: analysis of twenty-
semiology: report of the ILAE task force on classification and
one cases. Pediatr Neurol 2012;47(6):443e7.
terminology. Epilepsia 2001;42(9):1212e8.
27. Blume WT, Wiebe S, Tapsell LM. Occipital epilepsy: lateral
12. Boardman JP, Wusthoff CJ, Cowan FM. Hypoglycaemia and
versus mesial. Brain 2005;128(Pt 5):1209e25.
neonatal brain injury. Arch Dis Child Educ Pract Ed
28. Stephani U, Doose H. Benign idiopathic partial epilepsy and
2013;98(1):2e6.
brain lesion. Epilepsia 1999;40(3):373e6.
13. Anderson JM, Milner RD, Strich SJ. Effects of neonatal
29. Gelisse P, Corda D, Raybaud C, Dravet C, Bureau M, Genton P.
hypoglycaemia on the nervous system: a pathological study. J
Abnormal neuroimaging in patients with benign epilepsy
Neurol Neurosurg Psychiatry 1967;30(4):295e310.
with centrotemporal spikes. Epilepsia 2003;44(3):372e8.
14. Spar JA, Lewine JD, Orrison Jr WW. Neonatal hypoglycemia:
30. Yalcin AD, Toydaemir HE, Celebi LG, Forta H. Panayiotopoulos
CT and MR findings. AJNR Am J Neuroradiol 1994;15(8):1477e8.
syndrome with coincidental brain lesions. Epileptic Disord
15. Barkovich AJ, Ali FA, Rowley HA, Bass N. Imaging patterns of
2009;11(3):270e6.
neonatal hypoglycemia. AJNR Am J Neuroradiol
1998;19(3):523e8.

Please cite this article in press as: Arhan E, et al., Neonatal hypoglycemia: A wide range of electroclinical manifestations and seizure
outcomes, European Journal of Paediatric Neurology (2017), http://dx.doi.org/10.1016/j.ejpn.2017.05.009