Forensic Sci Med Pathol DOI 10.1007/s12024-014-9645-5
CASE REPORT
Fatal superior sagittal sinus hemorrhage as a complication of aplasia cutis congenita: a case report and literature review Rowena Johnson • Amaka Offiah • Marta C. Cohen
Accepted: 5 December 2014 Ó Springer Science+Business Media New York 2015
Abstract Aplasia cutis congenita (ACC) is a rare condition that occurs in around 0.01 % of births. Characterized by a localized absence of skin, it affects the midline of the scalp in over 80 % of cases. We describe the case of an infant born via vaginal spontaneous delivery with ACC affecting the scalp. This extended to the subcutaneous tissue and bone leaving the dura mater exposed. The patient was managed conservatively. At 4 weeks of age, she had a fatal superior sagittal sinus hemorrhage. In a review of the literature, we found ten previous cases of hemorrhage of the superior sagittal sinus complicating an ACC. Including our case, ACC complicated by hemorrhage of the superior sagittal sinus shows a 36 % mortality (4/11). An analysis of these cases suggests that this tends to occur between 1 and 3 months of age, though it may occur in younger neonates. Keywords Aplasia cutis congenita Hemorrhage Superior sagittal sinus
R. Johnson University of Sheffield, Sheffield, UK A. Offiah Academic Unit of Child Health, Room C4, Stephenson Wing Sheffield Children’s NHS Foundation Trust, Sheffield, UK M. C. Cohen (&) Histopathology Department, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK e-mail: [email protected]
Introduction Aplasia cutis congenita (ACC) is a rare condition that occurs in around 0.01 % of births [1–4]. Characterized by a localized absence of skin, it affects the midline of the scalp in over 80 % of cases, but may also be found on the face, limbs or trunk, commonly in a bilateral symmetrical pattern [2–5]. We hereby describe a fatal hemorrhage of the superior sagittal sinus complicating an isolated ACC in a 3 week old infant and review the literature of cases presenting with this infrequent condition.
Case report The infant described in this report was a term female born vaginally with a vertex presentation. Her birth weight was 2.3 kg indicating intrauterine growth restriction. The mother of the infant had a history of cleft lip and palate and was deaf, requiring hearing aids. There was also a history of learning difficulties in the family. At birth it was noted that the infant had an area of ACC, which affected the scalp. The deficit extended to the subcutaneous tissue and bone, leaving the dura mater exposed. Following conservative management the infant was discharged at 9 days old with a plan to perform reconstructive surgery over the following months and years. Three weeks later at 03:00 the 30-day-old infant started bleeding from the affected area of her scalp. Following telephone advice from the pediatric ward the bleeding was successfully controlled at home by applying pressure to the area. At 10:24 the same day, the infant was admitted to hospital as she had been sleepy, mottled, and feeding poorly since the previous day. The assessing doctor noticed blood actively gushing from the scalp and a pediatric crash
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On examination, the area of the ACC showed a heavily inflamed ulcer with central areas of necrosis that extended to the underlying dura mater and penetrated into the superior sagittal sinus immediately underneath this area. The dermis and adjacent dura mater showed the presence of granulation tissue and calcification, in keeping with a long-standing process (Fig. 2a, b). Microbiology of the brain and dura mater obtained scanty growth of Staphylococcus aureus along with light growth of Enterobacter cloacae from a brain swab. The postmortem skeletal survey did not reveal any significant skull vault abnormality. A whole body CT scan without contrast was also conducted. This clearly showed the abnormality of the superior portion of the skull with absence of bone. There was also widening of the metopic suture and the underlying bone was flattened (Fig. 3). The remaining skeleton was normal. Following postmortem investigation, the cause of death was concluded to be hypovolemic shock due to superior sagittal sinus hemorrhage complicating ACC.
team was called at approximately 11:05. Attempts to achieve hemostasis were unsuccessful and following several hours of resuscitative efforts it was concluded that the infant would never stabilize sufficiently to survive the surgery necessary to stop the hemorrhage. The decision was made to cease cardiac compressions and ventilation. Prior to extubation there was no cardiac output and pupils were fixed and dilated. The infant was declared dead at 15:40; at this time no surgery had taken place to manage the ACC. A medicolegal postmortem examination was conducted. The ACC was described as an absence of skin over an area of 4 cm 9 3 cm involving the vertex of the scalp. The defect extended deeper than the dermis, with absence of the subcutaneous tissue and no skull development in that area, leaving the dura mater exposed. The dura mater had a 2 mm 9 3 mm eroded area, which affected the superior sagittal sinus. This was determined to be the source of the bleeding (Fig. 1a). The infant had extreme paleness of the skin and mildly dysmorphic facial features, including a pointed chin and nose. No other significant pathological features were identified on external examination. Internal examination found pallor of the heart and liver but no other notable findings. The brain was removed leaving the dura mater and the area of aplasia cutis attached to it. Neuropathological examination was conducted after fixation in 20 % buffered formaldehyde. This revealed that the area of eroded dura mater opened into the superior sagittal sinus, which resulted in the massive hemorrhage (Fig. 1b). The brain appeared normally developed, though the cut surface was pale and soft, suggesting hypoxia. Histology identified congestion of the meninges but no evidence of acute infection. The neurones of the deep layers of the occipital cortex and CA4 area of the hippocampus showed signs of hypoxia.
ACC characterizes by a localized absence of skin, affecting the midline of the scalp in over 80 % of cases. There is some discrepancy in the literature over what exactly should be classified as ACC; while some studies suggest that only the epidermis may be absent, it is more commonly described as a total congenital absence of all skin layers [1, 3, 4, 6–8]. It was first described by Cordon in 1767, with the first scalp cases of ACC reported by Campbell in 1826 [9]. In some cases the lesion may extend beyond the skin with subcutaneous tissue involvement and in 20 % of cases the skull and dura mater are also affected, deeper involvement is associated with larger skin deficits
Fig. 1 a Macroscopic picture showing a skull defect underneath the area of aplasia cutis involving the vertex of the scalp, leaving the dura mater exposed. An ulcer was seen at the center of the area (arrow);
b the brain was removed and fixed with the dura matter attached. A closer inspection demonstrated that the ulcer connected with the superior sagittal sinus (see probe in situ)
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Fig. 2 a The ulcerated dura mater was heavily inflamed (short arrows) and communicated with the superior sagittal sinus underneath (long arrow); b the base of the ulcer showed granulation and calcification, in keeping with a long standing process
Fig. 3 Postmortem computed tomography: 3D-reconstructions on bony windows viewed from the back show widening of the fontanels and sagittal suture. Note the presence of ‘‘Wormian bones’’ along the sagittal suture (arrows). Soft tissue windows revealed no abnormality (note that contrast was not given for this postmortem CT study, therefore abnormality of the superior sagittal sinus would not be readily appreciated)
[1, 2, 4, 7]. This may result in the superior sagittal sinus being exposed and unprotected [2]. Previous cases have shown that in deep defects, a thin membrane covers the underlying sagittal sinus and brain and an ulcer may develop quickly after birth [7, 9–11]. In other instances, instead of a thin membrane, there may be a parchment-like membrane over the skin deficit or an ulcer of variable depth, which may extend to the skull and meninges [6, 12]. The skin deficit varies in shape but is typically round or oval and well demarcated [8, 13].
Histology of affected areas is not commonly studied and findings may vary [14]. Previous studies have shown that the histological features of the skin surrounding the defect may have reduced elastic fibers with a lack of dermal appendages and thinning of the epidermis [11, 15]. While being itself hairless, the deficit may be surrounded by the ‘‘hair collar sign’’—a ring of longer, thicker hair around the membrane [13]. These skin abnormalities may lead to scalp flap failure following surgical intervention [11]. In our case, there was a total absence of skin, dermis and skull in the affected area, while the presence of a heavily inflamed and infected ulcer obscured the histopathological assessment of the skin immediately surrounding the defect. This was so severe that it had ulcerated directly into the superior sagittal sinus, leading to the fatal hemorrhagic complication. The ACC is sometimes mistaken as an iatrogenic consequence of instrumental delivery [7]. This was not the case in our patient as she was born via vaginal spontaneous delivery. While this is not the case, the exact mechanism of this uncommon congenital condition is uncertain [4, 7]. It can occur as a genetic condition in an autosomal dominant pattern of varying penetrance and expression, and an autosomal recessive pattern has been observed more rarely [1, 2, 4, 16]. The family history along with the infant’s additional dysmorphic facial features reported at autopsy may indicate that this case of ACC might have genetic links. The infant’s DNA was stored to allow for further genetic analyses, which may enable parental advice on the risk of recurrence. However, ACC is most commonly sporadic and while hypotheses include mechanical or vascular events, intrauterine trauma, ectodermal arrest during embryogenesis and amniotic bands, the etiology remains uncertain [1, 2]. It has also been linked with intrauterine infection and
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Forensic Sci Med Pathol Table 1 Literature review of hemorrhage of the superior sagittal sinus complicating an aplasia cutis congenita Author
Year
Age at massive bleeding
Size lesion
Other features
Schneider et al. [24]
1980
7 weeks
7.5 9 7.5 cm
None reported
Glasson and Duncan [7]
1985
27 days
5 9 6 cm
None reported
Davis et al. [21]
1993
3 weeks
4 9 4 cm
Rudimentary toes and a short left index finger, suggestive of Adams–Oliver syndrome
Theile et al. [23]
1995
3 months
Large but not measurements provided
None reported
Ross et al. [25]
1995
13 weeks
10 9 10 cm
Features characteristic of Adams–Oliver syndrome: terminal transverse defects of the limbs, club like feet, syndactyly, and cutis marmorata
Kim et al. [20]
2001
1 month
7 9 2 cm
Hypoplasia of the pedal digits in keeping with Adams–Oliver syndrome
Koshy et al. [11]
2001
37 days
7 9 5 cm
None
Aloulou et al. [5]
2008
16 days
15 9 8 cm
Hypoplastic toes on right foot
Raposo-Amaral and Raposo-Amaral [22]
2011
2 months
4 9 4 cm
None
Mahmood et al. [6]
2012
5 days
Large but not measurements provided
None
Johnson et al. (this report)
2014
30 days
4 9 3 cm
None
exposure to carbimazole and methimazole, and other teratogens. Inheritance remains the only proven factor and it has previously been concluded that there is no single mechanism that leads to ACC [2–4, 14, 17]. While it may be an isolated malformation, ACC may occur along with other abnormalities such as omphalocele, clubfoot, cleft lip and palate, polycystic kidney, and trisomy 13 [2–4, 16–18]. It also occurs as part of Aplasia Cutis Congenita-Gastrointestinal, Johanson–Blizzard syndrome, and Adams–Oliver syndrome in which ACC, commonly of the skull, occurs alongside terminal transverse limb defects and cardiovascular malformations [17, 18]. Aplasia cutis has previously been classified into nine different types based on location, mode of inheritance and any associated abnormalities [14]. The extent of the deficit can also vary significantly, although usually less than 2 cm in diameter, much larger deficits of greater than 10 cm have been reported [5, 7]. Small lesions can be managed conservatively and will often resolve gradually, leaving a scar, skin contracture, alopecia, or varied pigmentation [9, 19, 20]. Larger lesions are more problematic, with a high risk of significant complications for which the optimum management is still debated [2]. Large skin deficits and lesions with involvement of the bone or dura mater can lead to
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biochemical abnormalities, infection, subdural thrombosis, and massive hemorrhage thought to occur in up to half of cases [1, 2, 15, 17, 19]. Mortality across all types of ACC is around 20 %, although some studies have reported this as varying from 10 to 60 % [2, 9]. Biochemical abnormalities such as hyponatremia and hyperkalemia may occur and may be caused by sulphadiazine dressings used to cover the skin deficit [20]. There is also the risk of infection and meningitis. As was found during postmortem microbiology investigations in this case, Staphylococcus aureus has been detected in scalp lesions in ACC cases as has Streptococcus pyogenes group A and Pseudomonas [11, 12, 15]. Oozing has been noted to be a possible sign of early infection [10]. Although hemorrhage is reported as a possible complication of ACC, there are only a small number of previous reports documenting this event (see Table 1). The literature describes ten previous cases of hemorrhage of the superior sagittal sinus complicating an ACC [5–7, 11, 20–25], with a mortality of 40 % (4/10). An analysis of these cases suggests that this tends to occur between 1 and 3 months of age, though it may occur in younger neonates [6, 17, 21]. In this context, the hemorrhage is often due to dissection and separation of the ulcerated tissue overlying the sagittal sinus, and consequently some authors have stressed that eschar formation
Forensic Sci Med Pathol Table 2 Treatment, complications, and outcome Author
Bleeding prior to surgical repair
Treatment
Survival
Schneider et al. [24]
Yes
Surgical repair of ruptured superior sagittal sinus, skin homografts
Yes
Glasson and Duncan [7]
Yes
Ligature of ruptured sagittal sinus, dural graft covered by a large right temporoparietal scalp flap. Necrotic complication was solved with a left temporoparietal scalp flap
Yesa
Davis et al. [21]
Yes
Combined neurosurgical and plastics procedure
Yes
Debrided and closed the defect, employing a rotation scalp flap and split skin graft Theile et al. [23]
No
Initially conservative. Then debridement, bilateral anteriorly based long scalp flaps and split skin grafting of the donor defects. Definitive reconstruction was by split rib cranioplasty to the extensive bony defect and a free latissimus dorsi muscle flap for soft tissue cover
Yes
Ross et al. [25]
No
Surgical ligation veins, conservative treatment allowing healing by secondary intention
No
Kim et al. [20]
Yes
Emergency ligature of ruptured superior sagittal sinus, eschar debridement, suture of dural defects, followed by occipital and temporoparietal flaps
Yes
Koshy et al. [11]
No
Initial paternal skin allograft, which failed. Scalp flap which became necrotic and infected
No
Aloulou et al. [5]
NA
Local care only
No
Raposo-Amaral and Raposo-Amaral [22]
Yes
Scalp flap and periosteum graft to cover dura mater defect
Yes
Mahmood et al. [6]
Yes
Surgical repair of the superior sagittal sinus, transposition flap, and split thickness skin graft
Yes
Johnson et al. (this report)
NA
Local care only
No
NA not applicable as surgery was not conducted a
With mental impairment due to complications of bleeding and surgical procedure
should be avoided by applying moist dressings to the affected area immediately following birth [10]. Certain dressings such as povidone iodine dressings can dry the defect leading to tearing and may increase the risk of sagittal sinus bleeding [17]. Bleeding can also be caused by ulceration eroding into the superior sagittal sinus or following surgical manipulation of the area [4, 6, 15]. Typically several small hemorrhages precede a major hemorrhage, as occurred in our case [9]. Hemorrhage has also been reported to occur following skin grafts if there continues to be a lack of bone growth; the majority of large skull deficits of greater than 6 cm rarely heal completely without intervention [10]. In our case, the patient was conservatively managed following telephone advice from the pediatric ward without a clinical examination. This may explain why the fatal complication was not diagnosed until the postmortem examination. The sudden death of this neonate, known to have ACC but in whom the fatal superior sagittal sinus hemorrhage was totally unsuspected, renders this case of particular relevance to the forensic pathologist. Successful treatment in those cases from the literature that survived [6, 7, 20–24] included emergency surgical repair of the
ruptured superior sagittal sinus, debridement, and scalp flaps (see Table 2). In our case, death was potentially preventable had surgical repair been conducted soon after diagnosis. Important differential diagnoses that the pathologist should bear in mind include inherited disorders of bone that are associated with Wormian bones and/or skull defects such as osteogenesis imperfecta, cleidocranial dysplasia and enlarged parietal foramina syndrome. In addition, the skull defect in this patient made the affected area more vulnerable to injury with minor trauma, requiring a differential diagnosis with non-accidental injury. In this case, knowledge that the infant had an area of ACC prompted CT head scanning (which was extended to include the entire body) in addition to the skeletal survey prior to the postmortem examination. The skeletal survey should be a routine part of the postmortem examination of any infant and a radiologist with experience of skeletal dysplasias should have no difficulty (as in this case) in excluding the typical fractures and intracranial hemorrhage of physical abuse; the reduced bone density, multiple Wormian bones, and slender and bowed bones of osteogenesis imperfecta; the hypoplastic clavicles, wide symphysis pubis and other characteristic skeletal findings of
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cleidocranial dysplasia and the paired (symmetrical) skull deficits of enlarged parietal foramina syndrome. If any doubts persist, then genetic mutation analysis is advised (Col1 mutations in the first instance for suspected OI, RUNX2 mutations in cleidocranial dysplasia and ALX4 and MSX2 mutations in parietal foramina syndrome) [26]. In summary, we describe an unusual case of ACC, which was complicated by an ulcer that eroded the superior sagittal sinus causing a fatal hemorrhage in a 4-week-old infant. Including our case, a total of 11 infants with hemorrhage of the superior sagittal sinus complicating aplasia cutis congenita have been described. This is an extremely unusual condition that carries a death rate of 36 % (4/11cases). An awareness of this potential complication may help prevent future fatalities.
Key points 1.
2.
3. 4.
5.
ACC is a rare congenital anomaly which can present to the forensic pathologist as a fatal hemorrhage of the superior sagittal sinus, usually presenting in a neonate. In order to diagnose this unusual complication, a detailed examination of the superior sagittal sinus should be conducted during the autopsy. The use of a postmortem CT scan has proved to be a useful diagnostic aid. ACC can present as an isolated malformation or be part of Adams–Oliver Syndrome, Aplasia Cutis Congenita-Gastrointestinal, or Johanson–Blizzard Syndrome. The differential diagnosis list includes non-accidental injury, Wormian bones and skull defects such as osteogenesis imperfecta, cleidocranial dysplasia and enlarged parietal foramina syndrome.
References 1. Bajpai M, Pal K. Aplasia cutis cerebri with partial acrania-total reconstruction in a severe case and review of the literature. J Pediatr Surg. 2003;38:e4. 2. Alexiou G, Sfakianos G, Prodromou N. Aplasia cutis congenita of the scalp. Turk Neurosurg. 2010;20:4–5. 3. Skoufi G, Lialio G, Plachouras N, Kutsogiannis D, Mperis A. Aplasia cutis congenita: successful conservative treatment. Pediatr Int. 2006;48:507–9. 4. O’Neill JK, Carter M, Warr RP. Aplasia cutis congenita. A case of scalp defect repair using two opposing bipedicled local flaps. J Plast Reconstr Aesthet Surg. 2010;63:e242–4.
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5. Aloulou H, Chaari W, Khanfir S, Zroud N, Kammoun TH, Abdelmoula M, Hachicha M. Aplasia cutis congenita du vertex (5 observations). Arch Pediatr. 2008;15:382–7. 6. Mahmood F, Tasneem S, Nadeem MM. Aplasia cutis congenita scalp presenting with life threatening hemorrhage: a case report. J Neonatal Surg. 2012;1:8. 7. Glasson DW, Duncan GM. Aplasia cutis congenita of the scalp: delayed closure complicated by massive hemorrhage. Plast Reconstr Surg. 1985;75:423–5. 8. Sanchez-Pedreno Guillen P, Rodriguez Pichardo A, Camacho Martinez F. Aplasia cutis congenita. J Am Acad Dermatol. 1985;13:429–33. 9. Sargent LA. Aplasia cutis congenita of the scalp. J Pediatr Surg. 1990;25:1211–3. 10. Yang JY, Yang WG. Large scalp and skull defect in aplasia cutis congenita. Br J Plast Surg. 2000;53:619–22. 11. Koshy CE, Waterhouse N, Peterson D. Large scalp and skull defects in aplasia cutis congenita. Br J Plast Surg. 2001;54:276–7. 12. Azad S, Falder S, Harrison J, Graham K. An adherent dressing for aplasia cutis congenita. Br J Plast Surg. 2005;58:1159–61. 13. Bellet JS. Developmental anomalies of the skin. Semin Perinatol. 2013;37:20–5. 14. Frieden IJ. Aplasia cutis congenita: a clinical review and proposal for classification. J Am Acad Dermatol. 1986;14:646–60. 15. Benjamin LT, Trowers AB, Schachner LA. Giant aplasia cutis congenita without associated anomalies. Pediatr Dermatol. 2004;21:150–3. 16. Colon-Fontanez F, Fallon Friedlander S, Newbury R, Eichenfield LF. Bullous aplasia cutis congenita. J Am Acad Dermatol. 2003;48:S95–8. 17. Santos de Oliveira R, Barros Juca´ CE, Lopes Lins-Neto A, et al. Aplasia cutis congenita of the scalp: is there a better treatment strategy? Childs Nerv Syst. 2006;22:1072–9. 18. Caksen H, Kurtoglu S. Our experience with aplasia cutis congenita. J Dermatol. 2002;29:376–9. 19. Saraiya HA. Management of aplasia cutis congenita of the scalp: a continuing enigma. Br J Plast Surg. 2002;55:707–8. 20. Kim CS, Tatum SA, Rodziewicz G. Scalp aplasia cutis congenita presenting with sagittal sinus hemorrhage. Arch Otolaryngol Head Neck Surg. 2001;127:71–4. 21. Davis PM, Buss PW, Simpson BA, Sykes PJ. Near fatal haemorrhage from the superior sagittal sinus in Adams–Oliver syndrome. Arch Dis Child. 1993;68:433. 22. Raposo-Amaral CE, Raposo-Amaral CA. Aplasia cutis congenita: impact of early treatment on calvarial osteogenesis. J Plast Reconstr Aesthet Surg. 2011;64:e237–40. 23. Theile RJ, Lanigan MW, McDermant GR. Reconstruction of aplasia cutis congenita of the scalp by split rib cranioplasty and a free latissimus dorsi muscle flap in a nine month old infant. Br J Plast Surg. 1995;48:507–10. 24. Schneider BM, Berg RA, Kaplan AM. Aplasia cutis congenita complicated by sagittal sinus hemorrhage. Pediatrics. 1980;66:948–50. 25. Ross DA, Laurie SW, Coombs CJ, Mutimer KL. Aplasia cutis congenita: failed conservative treatment. Plast Reconstr Surg. 1995;95:124–9. 26. Wyatt-Ashmead J, Konstantinidou A, Offiah AC. Skeletal dysplasias. In: Cohen MC, Scheimberg I, editors. The pediatric and perinatal autopsy manual. Cambridge: Cambridge University Press; 2014. p. 235–61.
CASE REPORT
Fatal superior sagittal sinus hemorrhage as a complication of aplasia cutis congenita: a case report and literature review Rowena Johnson • Amaka Offiah • Marta C. Cohen
Accepted: 5 December 2014 Ó Springer Science+Business Media New York 2015
Abstract Aplasia cutis congenita (ACC) is a rare condition that occurs in around 0.01 % of births. Characterized by a localized absence of skin, it affects the midline of the scalp in over 80 % of cases. We describe the case of an infant born via vaginal spontaneous delivery with ACC affecting the scalp. This extended to the subcutaneous tissue and bone leaving the dura mater exposed. The patient was managed conservatively. At 4 weeks of age, she had a fatal superior sagittal sinus hemorrhage. In a review of the literature, we found ten previous cases of hemorrhage of the superior sagittal sinus complicating an ACC. Including our case, ACC complicated by hemorrhage of the superior sagittal sinus shows a 36 % mortality (4/11). An analysis of these cases suggests that this tends to occur between 1 and 3 months of age, though it may occur in younger neonates. Keywords Aplasia cutis congenita Hemorrhage Superior sagittal sinus
R. Johnson University of Sheffield, Sheffield, UK A. Offiah Academic Unit of Child Health, Room C4, Stephenson Wing Sheffield Children’s NHS Foundation Trust, Sheffield, UK M. C. Cohen (&) Histopathology Department, Sheffield Children’s NHS Foundation Trust, Western Bank, Sheffield S10 2TH, UK e-mail: [email protected]
Introduction Aplasia cutis congenita (ACC) is a rare condition that occurs in around 0.01 % of births [1–4]. Characterized by a localized absence of skin, it affects the midline of the scalp in over 80 % of cases, but may also be found on the face, limbs or trunk, commonly in a bilateral symmetrical pattern [2–5]. We hereby describe a fatal hemorrhage of the superior sagittal sinus complicating an isolated ACC in a 3 week old infant and review the literature of cases presenting with this infrequent condition.
Case report The infant described in this report was a term female born vaginally with a vertex presentation. Her birth weight was 2.3 kg indicating intrauterine growth restriction. The mother of the infant had a history of cleft lip and palate and was deaf, requiring hearing aids. There was also a history of learning difficulties in the family. At birth it was noted that the infant had an area of ACC, which affected the scalp. The deficit extended to the subcutaneous tissue and bone, leaving the dura mater exposed. Following conservative management the infant was discharged at 9 days old with a plan to perform reconstructive surgery over the following months and years. Three weeks later at 03:00 the 30-day-old infant started bleeding from the affected area of her scalp. Following telephone advice from the pediatric ward the bleeding was successfully controlled at home by applying pressure to the area. At 10:24 the same day, the infant was admitted to hospital as she had been sleepy, mottled, and feeding poorly since the previous day. The assessing doctor noticed blood actively gushing from the scalp and a pediatric crash
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On examination, the area of the ACC showed a heavily inflamed ulcer with central areas of necrosis that extended to the underlying dura mater and penetrated into the superior sagittal sinus immediately underneath this area. The dermis and adjacent dura mater showed the presence of granulation tissue and calcification, in keeping with a long-standing process (Fig. 2a, b). Microbiology of the brain and dura mater obtained scanty growth of Staphylococcus aureus along with light growth of Enterobacter cloacae from a brain swab. The postmortem skeletal survey did not reveal any significant skull vault abnormality. A whole body CT scan without contrast was also conducted. This clearly showed the abnormality of the superior portion of the skull with absence of bone. There was also widening of the metopic suture and the underlying bone was flattened (Fig. 3). The remaining skeleton was normal. Following postmortem investigation, the cause of death was concluded to be hypovolemic shock due to superior sagittal sinus hemorrhage complicating ACC.
team was called at approximately 11:05. Attempts to achieve hemostasis were unsuccessful and following several hours of resuscitative efforts it was concluded that the infant would never stabilize sufficiently to survive the surgery necessary to stop the hemorrhage. The decision was made to cease cardiac compressions and ventilation. Prior to extubation there was no cardiac output and pupils were fixed and dilated. The infant was declared dead at 15:40; at this time no surgery had taken place to manage the ACC. A medicolegal postmortem examination was conducted. The ACC was described as an absence of skin over an area of 4 cm 9 3 cm involving the vertex of the scalp. The defect extended deeper than the dermis, with absence of the subcutaneous tissue and no skull development in that area, leaving the dura mater exposed. The dura mater had a 2 mm 9 3 mm eroded area, which affected the superior sagittal sinus. This was determined to be the source of the bleeding (Fig. 1a). The infant had extreme paleness of the skin and mildly dysmorphic facial features, including a pointed chin and nose. No other significant pathological features were identified on external examination. Internal examination found pallor of the heart and liver but no other notable findings. The brain was removed leaving the dura mater and the area of aplasia cutis attached to it. Neuropathological examination was conducted after fixation in 20 % buffered formaldehyde. This revealed that the area of eroded dura mater opened into the superior sagittal sinus, which resulted in the massive hemorrhage (Fig. 1b). The brain appeared normally developed, though the cut surface was pale and soft, suggesting hypoxia. Histology identified congestion of the meninges but no evidence of acute infection. The neurones of the deep layers of the occipital cortex and CA4 area of the hippocampus showed signs of hypoxia.
ACC characterizes by a localized absence of skin, affecting the midline of the scalp in over 80 % of cases. There is some discrepancy in the literature over what exactly should be classified as ACC; while some studies suggest that only the epidermis may be absent, it is more commonly described as a total congenital absence of all skin layers [1, 3, 4, 6–8]. It was first described by Cordon in 1767, with the first scalp cases of ACC reported by Campbell in 1826 [9]. In some cases the lesion may extend beyond the skin with subcutaneous tissue involvement and in 20 % of cases the skull and dura mater are also affected, deeper involvement is associated with larger skin deficits
Fig. 1 a Macroscopic picture showing a skull defect underneath the area of aplasia cutis involving the vertex of the scalp, leaving the dura mater exposed. An ulcer was seen at the center of the area (arrow);
b the brain was removed and fixed with the dura matter attached. A closer inspection demonstrated that the ulcer connected with the superior sagittal sinus (see probe in situ)
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Fig. 2 a The ulcerated dura mater was heavily inflamed (short arrows) and communicated with the superior sagittal sinus underneath (long arrow); b the base of the ulcer showed granulation and calcification, in keeping with a long standing process
Fig. 3 Postmortem computed tomography: 3D-reconstructions on bony windows viewed from the back show widening of the fontanels and sagittal suture. Note the presence of ‘‘Wormian bones’’ along the sagittal suture (arrows). Soft tissue windows revealed no abnormality (note that contrast was not given for this postmortem CT study, therefore abnormality of the superior sagittal sinus would not be readily appreciated)
[1, 2, 4, 7]. This may result in the superior sagittal sinus being exposed and unprotected [2]. Previous cases have shown that in deep defects, a thin membrane covers the underlying sagittal sinus and brain and an ulcer may develop quickly after birth [7, 9–11]. In other instances, instead of a thin membrane, there may be a parchment-like membrane over the skin deficit or an ulcer of variable depth, which may extend to the skull and meninges [6, 12]. The skin deficit varies in shape but is typically round or oval and well demarcated [8, 13].
Histology of affected areas is not commonly studied and findings may vary [14]. Previous studies have shown that the histological features of the skin surrounding the defect may have reduced elastic fibers with a lack of dermal appendages and thinning of the epidermis [11, 15]. While being itself hairless, the deficit may be surrounded by the ‘‘hair collar sign’’—a ring of longer, thicker hair around the membrane [13]. These skin abnormalities may lead to scalp flap failure following surgical intervention [11]. In our case, there was a total absence of skin, dermis and skull in the affected area, while the presence of a heavily inflamed and infected ulcer obscured the histopathological assessment of the skin immediately surrounding the defect. This was so severe that it had ulcerated directly into the superior sagittal sinus, leading to the fatal hemorrhagic complication. The ACC is sometimes mistaken as an iatrogenic consequence of instrumental delivery [7]. This was not the case in our patient as she was born via vaginal spontaneous delivery. While this is not the case, the exact mechanism of this uncommon congenital condition is uncertain [4, 7]. It can occur as a genetic condition in an autosomal dominant pattern of varying penetrance and expression, and an autosomal recessive pattern has been observed more rarely [1, 2, 4, 16]. The family history along with the infant’s additional dysmorphic facial features reported at autopsy may indicate that this case of ACC might have genetic links. The infant’s DNA was stored to allow for further genetic analyses, which may enable parental advice on the risk of recurrence. However, ACC is most commonly sporadic and while hypotheses include mechanical or vascular events, intrauterine trauma, ectodermal arrest during embryogenesis and amniotic bands, the etiology remains uncertain [1, 2]. It has also been linked with intrauterine infection and
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Forensic Sci Med Pathol Table 1 Literature review of hemorrhage of the superior sagittal sinus complicating an aplasia cutis congenita Author
Year
Age at massive bleeding
Size lesion
Other features
Schneider et al. [24]
1980
7 weeks
7.5 9 7.5 cm
None reported
Glasson and Duncan [7]
1985
27 days
5 9 6 cm
None reported
Davis et al. [21]
1993
3 weeks
4 9 4 cm
Rudimentary toes and a short left index finger, suggestive of Adams–Oliver syndrome
Theile et al. [23]
1995
3 months
Large but not measurements provided
None reported
Ross et al. [25]
1995
13 weeks
10 9 10 cm
Features characteristic of Adams–Oliver syndrome: terminal transverse defects of the limbs, club like feet, syndactyly, and cutis marmorata
Kim et al. [20]
2001
1 month
7 9 2 cm
Hypoplasia of the pedal digits in keeping with Adams–Oliver syndrome
Koshy et al. [11]
2001
37 days
7 9 5 cm
None
Aloulou et al. [5]
2008
16 days
15 9 8 cm
Hypoplastic toes on right foot
Raposo-Amaral and Raposo-Amaral [22]
2011
2 months
4 9 4 cm
None
Mahmood et al. [6]
2012
5 days
Large but not measurements provided
None
Johnson et al. (this report)
2014
30 days
4 9 3 cm
None
exposure to carbimazole and methimazole, and other teratogens. Inheritance remains the only proven factor and it has previously been concluded that there is no single mechanism that leads to ACC [2–4, 14, 17]. While it may be an isolated malformation, ACC may occur along with other abnormalities such as omphalocele, clubfoot, cleft lip and palate, polycystic kidney, and trisomy 13 [2–4, 16–18]. It also occurs as part of Aplasia Cutis Congenita-Gastrointestinal, Johanson–Blizzard syndrome, and Adams–Oliver syndrome in which ACC, commonly of the skull, occurs alongside terminal transverse limb defects and cardiovascular malformations [17, 18]. Aplasia cutis has previously been classified into nine different types based on location, mode of inheritance and any associated abnormalities [14]. The extent of the deficit can also vary significantly, although usually less than 2 cm in diameter, much larger deficits of greater than 10 cm have been reported [5, 7]. Small lesions can be managed conservatively and will often resolve gradually, leaving a scar, skin contracture, alopecia, or varied pigmentation [9, 19, 20]. Larger lesions are more problematic, with a high risk of significant complications for which the optimum management is still debated [2]. Large skin deficits and lesions with involvement of the bone or dura mater can lead to
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biochemical abnormalities, infection, subdural thrombosis, and massive hemorrhage thought to occur in up to half of cases [1, 2, 15, 17, 19]. Mortality across all types of ACC is around 20 %, although some studies have reported this as varying from 10 to 60 % [2, 9]. Biochemical abnormalities such as hyponatremia and hyperkalemia may occur and may be caused by sulphadiazine dressings used to cover the skin deficit [20]. There is also the risk of infection and meningitis. As was found during postmortem microbiology investigations in this case, Staphylococcus aureus has been detected in scalp lesions in ACC cases as has Streptococcus pyogenes group A and Pseudomonas [11, 12, 15]. Oozing has been noted to be a possible sign of early infection [10]. Although hemorrhage is reported as a possible complication of ACC, there are only a small number of previous reports documenting this event (see Table 1). The literature describes ten previous cases of hemorrhage of the superior sagittal sinus complicating an ACC [5–7, 11, 20–25], with a mortality of 40 % (4/10). An analysis of these cases suggests that this tends to occur between 1 and 3 months of age, though it may occur in younger neonates [6, 17, 21]. In this context, the hemorrhage is often due to dissection and separation of the ulcerated tissue overlying the sagittal sinus, and consequently some authors have stressed that eschar formation
Forensic Sci Med Pathol Table 2 Treatment, complications, and outcome Author
Bleeding prior to surgical repair
Treatment
Survival
Schneider et al. [24]
Yes
Surgical repair of ruptured superior sagittal sinus, skin homografts
Yes
Glasson and Duncan [7]
Yes
Ligature of ruptured sagittal sinus, dural graft covered by a large right temporoparietal scalp flap. Necrotic complication was solved with a left temporoparietal scalp flap
Yesa
Davis et al. [21]
Yes
Combined neurosurgical and plastics procedure
Yes
Debrided and closed the defect, employing a rotation scalp flap and split skin graft Theile et al. [23]
No
Initially conservative. Then debridement, bilateral anteriorly based long scalp flaps and split skin grafting of the donor defects. Definitive reconstruction was by split rib cranioplasty to the extensive bony defect and a free latissimus dorsi muscle flap for soft tissue cover
Yes
Ross et al. [25]
No
Surgical ligation veins, conservative treatment allowing healing by secondary intention
No
Kim et al. [20]
Yes
Emergency ligature of ruptured superior sagittal sinus, eschar debridement, suture of dural defects, followed by occipital and temporoparietal flaps
Yes
Koshy et al. [11]
No
Initial paternal skin allograft, which failed. Scalp flap which became necrotic and infected
No
Aloulou et al. [5]
NA
Local care only
No
Raposo-Amaral and Raposo-Amaral [22]
Yes
Scalp flap and periosteum graft to cover dura mater defect
Yes
Mahmood et al. [6]
Yes
Surgical repair of the superior sagittal sinus, transposition flap, and split thickness skin graft
Yes
Johnson et al. (this report)
NA
Local care only
No
NA not applicable as surgery was not conducted a
With mental impairment due to complications of bleeding and surgical procedure
should be avoided by applying moist dressings to the affected area immediately following birth [10]. Certain dressings such as povidone iodine dressings can dry the defect leading to tearing and may increase the risk of sagittal sinus bleeding [17]. Bleeding can also be caused by ulceration eroding into the superior sagittal sinus or following surgical manipulation of the area [4, 6, 15]. Typically several small hemorrhages precede a major hemorrhage, as occurred in our case [9]. Hemorrhage has also been reported to occur following skin grafts if there continues to be a lack of bone growth; the majority of large skull deficits of greater than 6 cm rarely heal completely without intervention [10]. In our case, the patient was conservatively managed following telephone advice from the pediatric ward without a clinical examination. This may explain why the fatal complication was not diagnosed until the postmortem examination. The sudden death of this neonate, known to have ACC but in whom the fatal superior sagittal sinus hemorrhage was totally unsuspected, renders this case of particular relevance to the forensic pathologist. Successful treatment in those cases from the literature that survived [6, 7, 20–24] included emergency surgical repair of the
ruptured superior sagittal sinus, debridement, and scalp flaps (see Table 2). In our case, death was potentially preventable had surgical repair been conducted soon after diagnosis. Important differential diagnoses that the pathologist should bear in mind include inherited disorders of bone that are associated with Wormian bones and/or skull defects such as osteogenesis imperfecta, cleidocranial dysplasia and enlarged parietal foramina syndrome. In addition, the skull defect in this patient made the affected area more vulnerable to injury with minor trauma, requiring a differential diagnosis with non-accidental injury. In this case, knowledge that the infant had an area of ACC prompted CT head scanning (which was extended to include the entire body) in addition to the skeletal survey prior to the postmortem examination. The skeletal survey should be a routine part of the postmortem examination of any infant and a radiologist with experience of skeletal dysplasias should have no difficulty (as in this case) in excluding the typical fractures and intracranial hemorrhage of physical abuse; the reduced bone density, multiple Wormian bones, and slender and bowed bones of osteogenesis imperfecta; the hypoplastic clavicles, wide symphysis pubis and other characteristic skeletal findings of
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Forensic Sci Med Pathol
cleidocranial dysplasia and the paired (symmetrical) skull deficits of enlarged parietal foramina syndrome. If any doubts persist, then genetic mutation analysis is advised (Col1 mutations in the first instance for suspected OI, RUNX2 mutations in cleidocranial dysplasia and ALX4 and MSX2 mutations in parietal foramina syndrome) [26]. In summary, we describe an unusual case of ACC, which was complicated by an ulcer that eroded the superior sagittal sinus causing a fatal hemorrhage in a 4-week-old infant. Including our case, a total of 11 infants with hemorrhage of the superior sagittal sinus complicating aplasia cutis congenita have been described. This is an extremely unusual condition that carries a death rate of 36 % (4/11cases). An awareness of this potential complication may help prevent future fatalities.
Key points 1.
2.
3. 4.
5.
ACC is a rare congenital anomaly which can present to the forensic pathologist as a fatal hemorrhage of the superior sagittal sinus, usually presenting in a neonate. In order to diagnose this unusual complication, a detailed examination of the superior sagittal sinus should be conducted during the autopsy. The use of a postmortem CT scan has proved to be a useful diagnostic aid. ACC can present as an isolated malformation or be part of Adams–Oliver Syndrome, Aplasia Cutis Congenita-Gastrointestinal, or Johanson–Blizzard Syndrome. The differential diagnosis list includes non-accidental injury, Wormian bones and skull defects such as osteogenesis imperfecta, cleidocranial dysplasia and enlarged parietal foramina syndrome.
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