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Varied presentation of lobar holoprosencephaly as a cause of macrocephaly in a neonate

Authors:
Amruta Varma at Datta Meghe Institute of Medical Sciences (Deemed University)
Amruta Varma
Rajasbala Dhande
Rajasbala Dhande
Gaurav V Mishra at Datta Meghe Institute of Higher Education and Research
Gaurav V Mishra
  • Datta Meghe Institute of Higher Education and Research
Bhushita Lakhkar at Datta Meghe Institute of Medical Sciences (Deemed University)
Bhushita Lakhkar
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Abstract

A 37 weeks primigravida presented in obstetric department with the report of labour pain. She had undergone antenatal scans two times; first scan in first trimester and second in third trimester. In the antenatal sonography at around 30 weeks, the fetus was diagnosed with hydrocephalus and macrocephaly.
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VarmaA, etal. BMJ Case Rep 2022;15:e248024. doi:10.1136/bcr-2021-248024
Varied presentation of lobar holoprosencephaly as a
cause of macrocephaly in aneonate
Amruta Varma ,1 Gaurav Vedprakash Mishra ,2 Rajasbala Dhande,2
Bhushita B Lakhkar3
Images in…
To cite: VarmaA, MishraGV,
DhandeR, etal. BMJ Case
Rep 2022;15:e248024.
doi:10.1136/bcr-2021-
248024
1Department of Radio- Diagnosis,
Datta Meghe Institute of
Medical Sciences—Wardha
Campus, Wardha, India
2Radiodiagnosis, Datta Meghe
Institute of Medical Sciences—
Wardha Campus, Wardha,
Maharashtra, India
3Radiology, Datta Meghe
Institute of Medical Sciences—
Wardha Campus, Wardha,
Maharashtra, India
Correspondence to
Dr Gaurav Vedprakash Mishra;
gaurav. mishra@ dmimsu. edu. in
Accepted 17 December 2021
© BMJ Publishing Group
Limited 2022. No commercial
re- use. See rights and
permissions. Published by BMJ.
DESCRIPTION
A 37 weeks primigravida presented in obstetric
department with the report of labour pain. She had
undergone antenatal scans two times; first scan in
first trimester and second in third trimester. In the
antenatal sonography at around 30 weeks, the fetus
was diagnosed with hydrocephalus and macro-
cephaly, as the head circumference was 31.5 cm,
which is >97 percentile for gestational age.1 On
examination, the cervix was 4 cm dilated and the
fetal head was not engaged. Considering the risk
of fetal distress and the presence of macrocephaly,
the patient was taken for caesarean section and
the baby was delivered at 37 weeks. The baby was
admitted in Neonatal Intensive Care Unit (NICU)
care in view of hyperbilirubinemia, serum bili-
rubin was 26.1 mg/dL, for which the phototherapy
was given. On clinical examination, the newborn
had occipitofrontal circumference of 41 cm, >97
percentile for the age2 and suggestive of macro-
cephaly. The baby also had downward gaze, frontal
bossing and was lethargic (figure 1). After 2 weeks,
the bilirubin levels were within normal limits and
the patient was advised MRI to rule out the cause
of hydrocephalus. On MRI, the findings of lobar
holoprosencephaly with enlargement of arachnoid
space were present: cavum septum was absent and
frontal horn of lateral ventricles were fused giving a
‘box- shaped appearance’.3 Interhemispheric fissure
and falx were present. There was partial fusion
of thalamus. Grey matter and white matter were
well appreciated with no gross atrophy of brain
parenchyma. All these features were suggestive of
lobar- type holoprosencephaly.4 However, along
with this, there were features of gross enlarge-
ment of subarachnoid space characterised by fluid
collection, which was similar to CSF intensity on
all the MRI sequences, that is, hyperintense on
T2WI and suppressed on FLAIR sequence. A vessel
traversing through this fluid collection was present,
suggestive of the ‘cortical vein sign’,5 thus, causing
the external hydrocephalus (figure 2).6 Following
this, peritoneal shunting of the fluid from the
external hydrocephalus caused due to the enlarged
subarachnoid spaces was done. Post drainage, there
was a decrease in head circumference, occipitof-
rontal circumference was 38 cm. The parents were
advised genetic testing for the baby as well as them-
selves, however, due to lack of financial support, it
was not done. The parents were advised regarding
the importance of timely antenatal scan as well, in
case of future pregnancy.
Figure 1 Neonate presenting with gross macrocephaly
and frontal bossing. No other external anomalies were
present.
Figure 2 (A)T2- weighted image on MRI showing the
presence of falx cerebri anteriorly (red arrow), absent
cavum septum and box- shaped fused frontal horns of
lateral ventricles (blue arrow) and traversing vessel
across the subarachnoid fluid collection giving cortical
vein sign(yellow arrow). (B)Post ventriculo- peritoneal
shunting CT image, showing the tip (arrow) of the
ventricular end in the enlarged subarachnoid space.
Patient’s perspective
Translated from patient’s mother’s language:
As soon as the labour pain started, I was
referred to the hospital where I delivered the baby.
Post the birth of my baby, we noticed her head was
enlarged, for which the doctor advised MRI. The
doctor informed us that the baby had an enlarged
head due to the collection of fluid and for which
shunting was done. I know that this is not common
and that the baby will have to be dependent on
others and have difficulty in performing routine
activities as she grows. I feel privileged hoping that
my baby’s story can help some other baby and the
parents who are suffering from the same.
by copyright. on January 19, 2022 at India:BMJ-PG Sponsored. Protectedhttp://casereports.bmj.com/BMJ Case Rep: first published as 10.1136/bcr-2021-248024 on 19 January 2022. Downloaded from
2VarmaA, etal. BMJ Case Rep 2022;15:e248024. doi:10.1136/bcr-2021-248024
Images in…
Acknowledgements I would like to thank Dr Sachin Yedve, Dr Soumya Jain and
Dr Subramanyam, who were involved in the patient care as well as in providing the
clinical details of the patient.
Contributors AV was involved in planning and reporting the work. GVM has
contributed in editing and formulating the case report. RD and BBL have contributed
in preparing the case report.
Funding The authors have not declared a specific grant for this research from any
funding agency in the public, commercial or not- for- profit sectors.
Competing interests None declared.
Patient consent for publication Consent obtained from parent(s)/guardian(s)
Provenance and peer review Not commissioned; externally peer reviewed.
Case reports provide a valuable learning resource for the scientific community and
can indicate areas of interest for future research. They should not be used in isolation
to guide treatment choices or public health policy.
ORCID iDs
AmrutaVarma http://orcid.org/0000-0001-5696-6304
Gaurav VedprakashMishra http://orcid.org/0000-0003-4957-7479
REFERENCES
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2 Grummer- Strawn LM, Reinold C, Krebs NF, etal. Use of World Health organization
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3 Winter TC, Kennedy AM, Woodward PJ. Holoprosencephaly: a survey of the entity, with
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4 Sikakulya FK, Kiyaka SM, Masereka R, etal. Alobar holoprosencephaly with
Cebocephaly in a neonate born to an HIV- positive mother in eastern Uganda. Case Rep
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5 Kuruvilla LC. Benign enlargement of sub- arachnoid spaces in infancy. J Pediatr Neurosci
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6 Marino MA, Morabito R, Vinci S, etal. Benign external hydrocephalus in infants.
Neuroradiol J 2014;27:245–50.
Learning points
►In case of holoprosencephaly, the cause of macrocephaly
is usually internal hydrocephalus; however, in this case,
it was the external hydrocephalus associated with
holoprosencephaly as an underlying cause of macrocephaly.
►Surgical shunting proved to be a life- saving procedure in
the present case where macrocephaly was unconventionally
caused due to external hydrocephalus. The proximal and
distal tip of the shunt were placed in subarachnoid space and
peritoneal cavity, respectively.
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... In HPE patients with normal head size or macrocephaly, hydrocephalus should be considered as the main cause [3,4]. Subdural hygroma or subarachnoid enlargement can also be found in HPE; however, it rarely causes macrocephaly [6]. ...
... HPE patients often have features of microcephaly. Macrocephaly can be found in HPE-associated hydrocephalus [3,4,6]. ...
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Background Severe macrocephaly can still be found in developing countries. This condition is usually caused by neglected hydrocephalus and can cause a lot of morbidities. Cranial vault reconstruction cranioplasty is the main treatment option for severe macrocephaly.Holoprosencephaly is often seen with features of microcephaly. Hydrocephalus should be considered as the main cause in HPE patients with features of macrocephaly. In this report, we present a rare case of cranial vault reduction cranioplasty procedure in patient with severe macrocephaly due to holoprosencephaly and subdural hygroma.Case descriptionA 4-year-10-month-old Indonesian boy was admitted with head enlargement since birth. He had a history of VP shunt placement when he was 3 months old. But the condition was neglected. Preoperative head CT showed massive bilateral subdural hygroma that compressed brain parenchyma caudally. From the craniometric calculation, the occipital frontal circumference was 70.5 cm with prominent vertex expansion, the distance between nasion to inion was 11.91 cm and the vertical height was 25.59 cm. The preoperative cranial volume was 24.611 cc. The patient underwent subdural hygroma evacuation and cranial vault reduction cranioplasty. The postoperative cranial volume was 10.468 cc.Conclusion Subdural hygroma can be a rare cause of severe macrocephaly in holoprosencephaly patients. Cranial vault reduction cranioplasty and subdural hygroma evacuation is still the main treatment option. Our procedure successfully reduces significant cranial volume (57.46% volume reduction).
View
Alobar Holoprosencephaly with Cebocephaly in a Neonate Born to an HIV-Positive Mother in Eastern Uganda
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Background: Holoprosencephaly (HPE) is a rare cerebrofacial abnormality resulting from the complete or partial failure of the diverticulation and cleavage of the primitive forebrain. It has an incidence at birth of 1:16000. Case Presentation. We report a case of a 2600 g newborn female delivered by an HIV-infected mother in whom an antenatal ultrasound scan at 34 weeks' gestation reported features of fetal alobar holoprosencephaly. The neonate was born with cebocephaly, a monkey-like head, and did not survive for more than 30 minutes following delivery by caesarian section despite oxygen therapy. Conclusion: Alobar HPE with cebocephaly remains incompatible with life. In this resource-limited setting, the diagnosis was made clinically, and only an ultrasound scan was performed to confirm the diagnosis. Chromosomal analysis could have given more information.
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The World Health Organization Fetal Growth Charts: A Multinational Longitudinal Study of Ultrasound Biometric Measurements and Estimated Fetal Weight
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Background Perinatal mortality and morbidity continue to be major global health challenges strongly associated with prematurity and reduced fetal growth, an issue of further interest given the mounting evidence that fetal growth in general is linked to degrees of risk of common noncommunicable diseases in adulthood. Against this background, WHO made it a high priority to provide the present fetal growth charts for estimated fetal weight (EFW) and common ultrasound biometric measurements intended for worldwide use. Methods and Findings We conducted a multinational prospective observational longitudinal study of fetal growth in low-risk singleton pregnancies of women of high or middle socioeconomic status and without known environmental constraints on fetal growth. Centers in ten countries (Argentina, Brazil, Democratic Republic of the Congo, Denmark, Egypt, France, Germany, India, Norway, and Thailand) recruited participants who had reliable information on last menstrual period and gestational age confirmed by crown–rump length measured at 8–13 wk of gestation. Participants had anthropometric and nutritional assessments and seven scheduled ultrasound examinations during pregnancy. Fifty-two participants withdrew consent, and 1,387 participated in the study. At study entry, median maternal age was 28 y (interquartile range [IQR] 25–31), median height was 162 cm (IQR 157–168), median weight was 61 kg (IQR 55–68), 58% of the women were nulliparous, and median daily caloric intake was 1,840 cal (IQR 1,487–2,222). The median pregnancy duration was 39 wk (IQR 38–40) although there were significant differences between countries, the largest difference being 12 d (95% CI 8–16). The median birthweight was 3,300 g (IQR 2,980–3,615). There were differences in birthweight between countries, e.g., India had significantly smaller neonates than the other countries, even after adjusting for gestational age. Thirty-one women had a miscarriage, and three fetuses had intrauterine death. The 8,203 sets of ultrasound measurements were scrutinized for outliers and leverage points, and those measurements taken at 14 to 40 wk were selected for analysis. A total of 7,924 sets of ultrasound measurements were analyzed by quantile regression to establish longitudinal reference intervals for fetal head circumference, biparietal diameter, humerus length, abdominal circumference, femur length and its ratio with head circumference and with biparietal diameter, and EFW. There was asymmetric distribution of growth of EFW: a slightly wider distribution among the lower percentiles during early weeks shifted to a notably expanded distribution of the higher percentiles in late pregnancy. Male fetuses were larger than female fetuses as measured by EFW, but the disparity was smaller in the lower quantiles of the distribution (3.5%) and larger in the upper quantiles (4.5%). Maternal age and maternal height were associated with a positive effect on EFW, particularly in the lower tail of the distribution, of the order of 2% to 3% for each additional 10 y of age of the mother and 1% to 2% for each additional 10 cm of height. Maternal weight was associated with a small positive effect on EFW, especially in the higher tail of the distribution, of the order of 1.0% to 1.5% for each additional 10 kg of bodyweight of the mother. Parous women had heavier fetuses than nulliparous women, with the disparity being greater in the lower quantiles of the distribution, of the order of 1% to 1.5%, and diminishing in the upper quantiles. There were also significant differences in growth of EFW between countries. In spite of the multinational nature of the study, sample size is a limiting factor for generalization of the charts. Conclusions This study provides WHO fetal growth charts for EFW and common ultrasound biometric measurements, and shows variation between different parts of the world.
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Use of World Health Organization and CDC growth charts for children aged 0-59 months in the United States
Article
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Holoprosencephaly: A Survey of the Entity, with Embryology and Fetal Imaging
Article
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  • Jan 2015
Structural malformations of the brain are an important cause of childhood mortality and morbidity, with the latter having long-term financial and psychosocial implications for the affected child and family. Holoprosencephaly (HPE) is a severe brain malformation characterized by abnormal cleavage of the prosencephalon in the 5th gestational week. Aprosencephaly and atelencephaly occur earlier because of failure in the formation of the prosencephalon and telencephalon, respectively. The HPE spectrum classically includes alobar, semilobar, and lobar forms, although there are no clear-cut defining features. The middle interhemispheric variant (MIH), also known as syntelencephaly, is classified as a variant of HPE with midline interhemispheric fusion. Other conditions sometimes included in the spectrum of HPE include septo-optic dysplasia (SOD); "minimal" HPE, which is associated with subtle craniofacial malformations and mild developmental delay; and microform HPE, which by definition excludes brain involvement. The focus of this article will be on the spectrum of findings visible in fetal manifestation of the HPE spectrum. Brain embryology; the imaging characteristics, epidemiology, and embryology of HPE; and the more common associated anomalies, particularly those of the face ("the face predicts the brain") are reviewed. Recognition of these anomalies is important for accurate parental counseling, since the prognosis is poor but not invariably lethal; children with the milder forms may live well into their teens with severe developmental delays, endocrine dysfunction, and disrupted homeostasis. Available data on outcome in surviving children are summarized. Illustrative fetal ultrasonographic and magnetic resonance images are presented with clinical, autopsy, and postnatal imaging correlation. (C) RSNA, 2015
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Benign enlargement of sub-arachnoid spaces in infancy
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Benign enlargement of sub-arachnoid spaces (BESS) is one of the causes of macrocephaly in infants. It is a self-limiting condition and does not require any active medical or surgical treatment. We report a case of an infant aged 4 months who was referred for magnetic resonance imaging (MRI) of the brain as the head circumference of the infant had increased rapidly from the 50(th) percentile in the 3(rd) month to more than the 95(th) percentile in the 4(th) month of age. MRI revealed enlarged anterior sub-arachnoid spaces and mild prominence of all the ventricles. A possibility of BESS was suspected since the child was neurodevelopmentally normal. A follow-up MRI done at the age of 18 months showed a reduction in the size of the sub-arachnoid spaces with normal sized ventricles.
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Benign External Hydrocephalus in Infants: A Single Centre Experience and Literature Review
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External hydrocephalus (EH) is a benign clinical entity in which macrocephaly is associated with an increase in volume of the subarachnoid space, especially overlying both frontal lobes, and a normal or only slight increase in volume of the lateral ventricles. Several pathogenic hypotheses have been proposed but the most accredited theory seems to be delayed maturation of the arachnoid villi. There is a consensus that this is a benign entity, correlated to a familial predisposition and, in some cases, inheritance. CT and MRI are very important to make a diagnosis but also to establish the prognosis in patients who encounter the rare complications such as subdural haematomas. In conclusion, CT and MRI can provide a highly accurate diagnosis in these patients, allowing a preliminary assessment of the prognosis, particularly regarding the enlarged subarachnoid space limits and the "cortical vein" sign which can predict a further complication. These results are obtained with the same examination performed in a standard CT or MRI study of the brain and no injection of contrast medium is needed.
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Benign external hydrocephalus in infants
  • Jan 2014
  • 245-50
  • MA Marino
  • R Morabito
  • S Vinci
Marino MA, Morabito R, Vinci S, et al. Benign external hydrocephalus in infants. Neuroradiol J 2014;27:245-50.