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Differential diagnosis between traumatic and nontraumatic rupture of the intracranial vertebral artery in medicolegal autopsy
Legal Medicine 11 (2009) S66–S70
Contents lists available at ScienceDirect
Legal Medicine journal homepage: www.elsevier.com/locate/legalmed
Review Article
Differential diagnosis between traumatic and nontraumatic rupture of the intracranial vertebral artery in medicolegal autopsy Ayako Ro a,b,*, Norimasa Kageyama b, Akihiro Takatsu b, Tatsushige Fukunaga b a b
Department of Legal Medicine, School of Medicine, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Tokyo Medical Examiner’s Office, Tokyo Metropolitan Government, Tokyo 112-0012, Japan
a r t i c l e
i n f o
Article history: Received 13 December 2008 Received in revised form 10 February 2009 Accepted 16 February 2009 Available online 2 April 2009 Keywords: Subarachnoid hemorrhage Arterial dissection Intracranial vertebral artery Head injury Histopathology Autopsy
a b s t r a c t We attempted to establish histopathological identification between traumatic rupture and nontraumatic arterial dissection of the intracranial vertebral artery (IVA) resulting in subarachnoid hemorrhage (SAH). Step-serial observations of ruptured IVAs among four traumatic and 44 nontraumatic SAH patients were investigated. We found that the most specific characteristic for differentiation was the shape of the ruptured adventitia. Extension of the adventitia was clearly observed in nontraumatic cases. In contrast, traumatic cases showed transmural ruptures. Other specific characteristics were also detected. For traumatic cases, small incomplete tears of intima and media were frequently found; they formed oblique tears without adventitial extension. Fragmentized internal elastic lamina was also observed in traumatic cases. In contrast, previous arterial dissections were frequently confirmed in nontraumatic cases. Medial degenerations or defects were detected in all nontraumatic cases. In these cases, the peripheral lesion of the rupture was appeared as intimal tears at recessed vascular wall caused by medial defects. This suggested a relationship between medial lesions and pathogenesis of arterial dissections. These additional features were found in both ruptured and non-ruptured intracranial arteries. We concluded that histopathological investigation is a reliable method for differential diagnosis between traumatic and nontraumatic rupture of the IVA resulting in fatal SAH. These morphological differentiations could be valuable for medicolegal diagnosis. Ó 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Subarachnoid hemorrhage (SAH) due to a ruptured intracranial vertebral artery (IVA) is a serious disease, which may cause sudden fatal outcome. In medicolegal autopsy, traumatic rupture of IVA (TRIVA) can occur as a result of a relatively small external force applied to the neck or head without brain contusion or skull fractures [1–4]. In contrast, IVA is also a favorite site of nontraumatic intracranial artery dissection [5–7]. Therefore, it is difficult to differentiate between traumatic and nontraumatic rupture of the IVA in medicolegal autopsy cases of SAH associated with slight blunt trauma. In this report, we attempted to establish histopathological differentiation between two alternative pathogeneses.
IVA. Among them, four cases were diagnosed as TRIVA; their clinical and autopsy summary are shown in Table 1. The remaining 40 cases were nontraumatic intracranial vertebral artery dissection (NIVAD) without a history of head or neck injury. After macroscopic examination, the whole intracranial artery was removed from the brain and fixed with formalin. The ruptured IVA was embedded in paraffin blocks. Duplicate 5-lm cross-sections from each 0.2 mm segment were cut and put on slides, and then stained with hematoxylin and eosin and Elastica van Gieson. Other areas of the intracranial artery were histopathologically observed at several locations. 3. Results
2. Materials and methods
3.1. Macroscopic findings
Histopathological investigations using step-serial sections were performed on 44 medicolegal autopsy cases of SAH due to ruptured
All cases were diffuse SAH, especially around the cerebral base (Fig. 1). Among the TRIVA cases, neither skull fractures nor brain contusions were detected, except for one case with a skull fracture. The ruptured sites were in the middle portion of the IVA. There was a longitudinal rupture in each of the TRIVA and NIVAD cases. NIVAD cases showed fusiform aneurysm, which was barely distinguishable macroscopically from TRIVA cases.
* Corresponding author. Address: Department of Legal Medicine, School of Medicine, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Tel.: +81 3 5269 7300; fax: +81 3 5269 7300. E-mail address: [email protected] (A. Ro). 1344-6223/$ - see front matter Ó 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.legalmed.2009.02.067
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A. Ro et al. / Legal Medicine 11 (2009) S66–S70 Table 1 Clinical summary and autopsy findings of four cases of TRIVA. Case
Age
Sex
Nature of trauma
Survival time
Ruptured IVAa
Other head injury
1 2 3 4
55 43 14 49
M M M M
Fist blows to the face Fist and umbrella blows to the face Fist blow to the neck Crushing of the body inside a car and impact on the road
3 days: unconscious immediately 6 days: unconscious immediately 28 days: unconscious immediately 2.5 h
Left Left Left Left Right
None None None Skull fracture
a
IVA, intracranial vertebral artery.
Fig. 1. Representative cases of TRIVA (a–c) and NIVAD (d–f). (a) Macroscopic appearance of TRIVA at the cerebral base after removal of superficial blood. (b) Macroscopic appearance of IVAs. Arrows indicate the ruptured site at bilateral IVAs. (c) Scheme of longitudinal rupture of TRIVA. (d) Macroscopic appearance of NIVAD at the cerebral base after removal of superficial blood. (e) Macroscopic appearance of IVAs. Arrow indicates ruptured site with fusiform aneurysm. (f) Scheme of longitudinal rupture of NIVAD.
3.2. Histopathological findings in the ruptured area The most specific histopathological characteristic that we found for differentiation between TRIVA and NIVAD cases was detected in the ruptured adventitia (Fig. 2). All TRIVA cases were transmural rupture without extension of the adventitia. On the other hand, extension of the adventitia was observed in all NIVAD cases. 3.3. Histopathological findings of the peripheral lesion of the rupture In TRIVA cases, an oblique tear of the intima and media was observed at the peripheral lesion of the rupture (Fig. 3). In contrast, in NIVAD cases, the intimal tear occurred at the recessed vascular wall according to massive medial defect. 3.4. Additional histopathological findings in non-ruptured lesions Several specific characteristics were detected for each of the following conditions. In TRIVA cases, the numbers of small incomplete tears of the intima or media were frequently observed without extension of the adventitia (Fig. 4a). Fragmentation of internal elastic lamina was also observed in TRIVA cases (Fig. 4b). In contrast, previous arterial dissections were sometimes detected in NIVAD cases (Fig. 4c). Medial degeneration or defects were observed in all NIVAD cases (Fig. 4d). These features were not always
observed; however, it usually confirmed as specific features of either case. Furthermore, these features were observed not only in ruptured IVAs but also in contralateral IVAs or other intracranial arteries.
4. Discussion Several different etiologies are believed to be involved in the case of SAH due to ruptured IVA: (1) traumatic rupture of the intact IVA by external force, (2) spontaneous rupture of an IVA aneurysm or dissection, (3) rupture of a latent IVA aneurysm or dissection by external force, and (4) delayed rupture of a traumatic intracranial aneurysm. In this report, we focused our investigation on the former two conditions. Isolated traumatic SAH is an infrequent consequence of fatal head injuries in approximately 3.4–11% cases in medicolegal autopsy [2,4]. Tatsuno and Lindenberg proposed several mechanisms for tearing of intracranial arteries: short duration oscillations of the brain, stretching force from hyperextension, and a momentary increase in intra-arterial pressure as a result of a blow to the carotid artery in the neck [8]. Isolated traumatic SAH is usually caused by a traumatic rupture of the IVA or in other posterior circulations [1–4]. TRIVA can occur by a small injury such as a single strike to the neck or head. TRIVA tends to cause diffuse basal
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Fig. 2. Histological characteristics of the ruptured site. Each of the histopathological photos of TRIVA and NIVAD cases are the same cases as shown in Fig. 1. Arrows indicate adventitia and arrowheads indicate intima of the ruptured site. (a) Scheme of the ruptured site of TRIVA. (b) Microscopic photo of the ruptured site of TRIVA (Elastica van Gieson stain). It was a transmural rupture without extension of the adventitia. (c) cheme of the ruptured site of NIVAD. (d) Microscopic photo of the ruptured site of NIVAD (Elastica van Gieson stain). The adventitia was widely extended by the medial dissecting hematoma.
Fig. 3. Histological characteristics of the peripheral lesion of the intimal tear. (a) Scheme of the peripheral lesion of TRIVA. (b) Microscopic photo of the peripheral lesion of TRIVA (Elastica van Gieson stain). It was an oblique tear of the intima and media. (c) Scheme of the peripheral lesion of NIVAD. (d) Microscopic photo of the peripheral lesion of NIVAD (Elastica van Gieson stain). The intimal tear occurred at the recessed vessel wall according to a massive medial defect.
SAH without serious skull fracture or brain contusion. Therefore, if postmortem head computer tomography was performed, it would show that the diffuse basal SAH is indistinguishable from TRIVA and NIVAD. Therefore, differential diagnosis between TRIVA and NIVAD still remains a medicolegal problem. Usually, TRIVA has been diagnosed by referring to circumstances before death, such as the existence of neck or head injury. However, we sometimes experience fatal NIVAD cases accompanied by consecutive head injury [9]. Otherwise, macroscopic appearance of longitudinal ruptures of IVA is considered as a characteristic of TRIVA [10]. However, longitudinal ruptures were de-
tected in both TRIVA and NIVAD cases in this study. Therefore, another method is required for differential diagnosis between TRIVA and NIVAD. In the current study, we attempted to establish histopathological identification between TRIVA and NIVAD (Table 2) [11,12]. The step-serial observations showed that the most specific characteristic for differentiation between TRIVA and NIVAD was the shape of the ruptured adventitia. Extension of the adventitia was clearly observed at the ruptured lesion in every NIVAD case. This finding suggests that there is a time lag between a medial dissecting hematoma and fatal rupture of the adventitia in NIVAD cases.
A. Ro et al. / Legal Medicine 11 (2009) S66–S70
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Fig. 4. Additional characteristic findings of non-ruptured areas. (a) Small incomplete tears of the intima and media (arrows) in a TRIVA case (Elastica van Gieson stain). (b) Fragmentized internal elastic lamina(arrow) in a TRIVA case (Elastica van Gieson stain). (c) Previous NIVAD (asterisk) in a NIVAD case (Elastica van Gieson stain). (d) Medial degeneration (arrows) in a NIVAD case (Elastica van Gieson stain). Table 2 Macroscopic and histopathological characteristics of TRIVA and NIVAD. TRIVAa
NIVADb
Longitudinal rupture
Fusiform aneurysm with longitudinal rupture
Transmural arterial rupture Not extended Oblique tear of the intima and media
Arterial dissection
Macroscopic appearance
Histopathological findings Ruptured site Appearance Adventitia Peripheral lesion Non-ruptured site Additional findings(not always present)
Small incomplete tears Fragmentized internal elastic lamina
a b
Extended Intimal tear according to medial defect Previous non-ruptured dissection Medial degeneration or defect
TRIVA, traumatic rupture of the intracranial vertebral artery. NIVAD, nontraumatic intracranial vertebral artery dissection.
In contrast, TRIVA showed a trilaminar transmural rupture, which occurred at the same time as the head injury. These specific features were confirmed in every TRIVA case. We propose that histopathological observation of the adventitia at a ruptured lesion is a novel differential viewpoint between TRIVA and NIVAD. Additionally, other specific characteristics for each condition were detected by histopathological examination. For TRIVA, small incomplete tears of the intima and media were frequently found in both ruptured and non-ruptured lesions. They formed oblique tears without extension of adventitia. The peripheral lesion of the rupture also appeared as oblique tears. In addition, as a result of multiple tears, a fragmentized internal elastic lamina was also observed in TRIVA cases. Fragmentation of the internal elastic lamina or small intimal damage of the intracranial artery have been proposed as additional histopathological findings of brain injury by some researchers [1,13,14]. These findings would be useful in the case of delayed fatal sequelae [15]. In our case, even one month later after IVA injury, oblique tears or fragmentized internal elastic
lamina were confirmed despite the effect of vascular repairing process. NIVAD usually occurs in middle aged men with hypertension [7,16]. It may cause recurrent dissections occurring in bilateral IVAs with spontaneous resolutions [7]. Previous NIVADs were confirmed as a repaired medial hematoma organized by collagen fibers accompanied by small tears of the internal elastic lamina. In this study, previous dissections were frequently confirmed at both ruptured and non-ruptured intracranial arteries in NIVAD cases. In addition, prodromal symptoms related to arterial dissections such as head or neck pain were often complained of before lethal attacks in NIVAD cases. Our previous study of 58 NIVAD cases revealed that previous IVA dissection was detected in 43% and that prodromal symptoms related to IVA dissections were detected in 43%[16].Such clinical symptoms prior to death might be helpful for diagnosis as NIVAD. With regard to other histopathological characteristics of NIVAD, medial degenerations or defects were detected in all NIVAD cases in this study. In addition, the peripheral lesion of the rupture appeared as intimal tears at the recessed vascular wall caused by a massive medial defect. It is believed that medial degenerations or defects result in the pathogenesis of NIVAD [9,12,17,18].The pathogenesis of NIVAD remains unclear. Further investigation is required to determine the role that medial lesions play in the mechanism of NIVAD. Finally, we would like to emphasize the importance of histopathological examination of intracranial arteries for differentiation between TRIVA and NIVAD in medicolegal autopsy cases of ruptured vertebral arteries. The reference of circumstance before death such as an existence of head injury or prodromal symptom is important but obscure for objective differentiation. Furthermore, it is very difficult to differentiate between TRIVA and NIVAD by macroscopic findings. Histopathological characteristics such as those described in this paper could offer objective differentiation among the two alternative conditions. Investigations using stepserial sections are also desirable for reliable observation [14] because medial defects or small incomplete tears resemble technical artifacts. Additionally, other histopathological characteristics of both TRIVA and NIVAD were detected at non-ruptured areas in the intracranial artery. Histopathological investigation of not only
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ruptured sites but also of non-ruptured cerebral arteries is strongly recommended. In conclusion, histopathological investigation using step-serial sections is a reliable method for differential diagnosis between traumatic rupture and nontraumatic intracranial artery dissections occurring at the IVA resulting in fatal SAH. The most striking histopathological feature was adventitial extension at the ruptured site in nontraumatic cases. Additional histopathological characteristics for each pathogenesis were confirmed not only in ruptured IVAs but also in non-ruptured IVAs. These morphological differentiations could be valuable for medicolegal diagnosis in cases of SAH due to a ruptured IVA. Conflict of interest This study was supported in part by the Grant-in-Aid for Scientific Research for Young Scientists to Ayako Ro, M.D., Ph.D(19790448). The funding source had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. References [1] Dowling G, Curry B. Traumatic basal subarachnoid hemorrhage report of six cases and review of the literature. Am J Forensic Med Pathol 1988;9:23–31. [2] Okada Y, Mukaida M, Mori A, Tanabe R, Ishiyama I. Isolated traumatic subarachnoid hemorrhage. Jpn J Traumatol Occup Med 1989;37:279–85. [3] Bunai Y, Nagai A, Nakamura I I, Ohya I. Traumatic rupture of the basilar artery: report of two cases and review of the literature. Am J Forensic Med Pathol 2000;21:343–8. [4] Hiraiwa K, Sato T, Sasaki T, Mizusawa I, Nata M, Kodama N. Medico-legal aspects of traumatic injury of the vertebrobasilar artery. Neurol Med Chir (Tokyo) 2005;45:549–55. [5] Murai T, Baba M, Ro A, Murai N, Matsuo Y, Takada A, et al. Sudden death due to cardiovascular disorders: a review of the studies on the medico-legal cases in Tokyo. Keio J Med 2001;50:175–81.
[6] Murai T, Saito K, Takada A, Murai N, Yabe K, Hara M, et al. Subarachnoid hemorrhage from ruptured dissecting aneurysm of vertebral artery: a clinicopathological study. Res Pract Forensic Med 1993;36:175–83 [in Japanese with English abstract]. [7] Yamaura A, Ono J, Hirai S. Clinical picture of intracranial non-traumatic dissecting aneurysm. Neuropathology 2000;20:85–90. [8] Tatsuno Y, Lindenberg R. Basal subarachnoid hematomas as sole intracranial traumatic lesions. Arch Pathol 1974;97:211–5. [9] Ro A, Kageyama N, Hayashi K, Shigeta A, Fukunaga T. Non-traumatic rupture of the intracranial vertebral artery of a man found dead in a severe car accident histopathological differentiation by step-serial sections. Legal Med (Tokyo) 2008;10:101–6. [10] Miyazaki T, Kojima T, Chikasue F, Yashikie M, Ito H. Traumatic rupture of intracranial vertebral artery due to hyperextension of the head: reports on three cases. Forensic Sci Int 1990;47:91–8. [11] Ro A, Kageyama N, Fukunaga T, Hisashi Y, Murai T, Fujita MQ. Differential diagnosis of ruptured vertebral arteries: (1) Characters of traumatic ruptures. Rechtsmedizin 2005;15:333. [12] Kageyama N, Ro A, Fukunaga T, Murai T. Differential diagnosis of ruptured vertebral arteries: (2) Characteristics of idiopathic arterial dissection. Rechtsmedizin 2005;15:333–4. [13] Djokic V, Savic S, Atanasijevic T. Medicolegal diagnostic value and clinical significance of traumatic incomplete tears of the basilar artery. Am J Forensic Med Pathol 2003;24:208–13. [14] Pollanen MS, Deck JH, Blenkinsop B. Injury of the tunica media in fatal rupture of the vertebral artery. Am J Forensic Med Pathol 1996;17:197–201. [15] Sahjpaul RL, Abdulhak MM, Drake CG, Hammond RR. Fatal traumatic vertebral artery aneurysm rupture. Case report. J Neurosurg 1998;89:822–4. [16] Ro A, Kageyama N, Abe N, Takatsu A, Fukunaga T.Intracranial vertebral arterial dissection resulting in fatal subarachnoid hemorrhage: clinical and histopathological investigations from a medicolegal perspective. J Neurosurg, published online February 6, 2009, doi:10.3171/2008.11. JNS08951. [17] Kageyama N, Abe N, Kurosu K, Tanifuji T, Takada A, Saito K, et al. A pathological study of dissecting aneurysm of the intracranial vertebral artery – three dimensional structure of the vertebral artery. Res Pract Forensic Med 2002;45:75–9 [in Japanese with English abstract]. [18] Ro A, Kageyama N, Takatsu A, Fukunaga T. Segmental arterial mediolysis of varying phases affecting both the intraabdominal and intracranial vertebral arteries: an autopsy case report. Cardiovasc Pathol, 2009. doi:10.1016/ j.carpath.2009.02.002.
Contents lists available at ScienceDirect
Legal Medicine journal homepage: www.elsevier.com/locate/legalmed
Review Article
Differential diagnosis between traumatic and nontraumatic rupture of the intracranial vertebral artery in medicolegal autopsy Ayako Ro a,b,*, Norimasa Kageyama b, Akihiro Takatsu b, Tatsushige Fukunaga b a b
Department of Legal Medicine, School of Medicine, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan Tokyo Medical Examiner’s Office, Tokyo Metropolitan Government, Tokyo 112-0012, Japan
a r t i c l e
i n f o
Article history: Received 13 December 2008 Received in revised form 10 February 2009 Accepted 16 February 2009 Available online 2 April 2009 Keywords: Subarachnoid hemorrhage Arterial dissection Intracranial vertebral artery Head injury Histopathology Autopsy
a b s t r a c t We attempted to establish histopathological identification between traumatic rupture and nontraumatic arterial dissection of the intracranial vertebral artery (IVA) resulting in subarachnoid hemorrhage (SAH). Step-serial observations of ruptured IVAs among four traumatic and 44 nontraumatic SAH patients were investigated. We found that the most specific characteristic for differentiation was the shape of the ruptured adventitia. Extension of the adventitia was clearly observed in nontraumatic cases. In contrast, traumatic cases showed transmural ruptures. Other specific characteristics were also detected. For traumatic cases, small incomplete tears of intima and media were frequently found; they formed oblique tears without adventitial extension. Fragmentized internal elastic lamina was also observed in traumatic cases. In contrast, previous arterial dissections were frequently confirmed in nontraumatic cases. Medial degenerations or defects were detected in all nontraumatic cases. In these cases, the peripheral lesion of the rupture was appeared as intimal tears at recessed vascular wall caused by medial defects. This suggested a relationship between medial lesions and pathogenesis of arterial dissections. These additional features were found in both ruptured and non-ruptured intracranial arteries. We concluded that histopathological investigation is a reliable method for differential diagnosis between traumatic and nontraumatic rupture of the IVA resulting in fatal SAH. These morphological differentiations could be valuable for medicolegal diagnosis. Ó 2009 Elsevier Ireland Ltd. All rights reserved.
1. Introduction Subarachnoid hemorrhage (SAH) due to a ruptured intracranial vertebral artery (IVA) is a serious disease, which may cause sudden fatal outcome. In medicolegal autopsy, traumatic rupture of IVA (TRIVA) can occur as a result of a relatively small external force applied to the neck or head without brain contusion or skull fractures [1–4]. In contrast, IVA is also a favorite site of nontraumatic intracranial artery dissection [5–7]. Therefore, it is difficult to differentiate between traumatic and nontraumatic rupture of the IVA in medicolegal autopsy cases of SAH associated with slight blunt trauma. In this report, we attempted to establish histopathological differentiation between two alternative pathogeneses.
IVA. Among them, four cases were diagnosed as TRIVA; their clinical and autopsy summary are shown in Table 1. The remaining 40 cases were nontraumatic intracranial vertebral artery dissection (NIVAD) without a history of head or neck injury. After macroscopic examination, the whole intracranial artery was removed from the brain and fixed with formalin. The ruptured IVA was embedded in paraffin blocks. Duplicate 5-lm cross-sections from each 0.2 mm segment were cut and put on slides, and then stained with hematoxylin and eosin and Elastica van Gieson. Other areas of the intracranial artery were histopathologically observed at several locations. 3. Results
2. Materials and methods
3.1. Macroscopic findings
Histopathological investigations using step-serial sections were performed on 44 medicolegal autopsy cases of SAH due to ruptured
All cases were diffuse SAH, especially around the cerebral base (Fig. 1). Among the TRIVA cases, neither skull fractures nor brain contusions were detected, except for one case with a skull fracture. The ruptured sites were in the middle portion of the IVA. There was a longitudinal rupture in each of the TRIVA and NIVAD cases. NIVAD cases showed fusiform aneurysm, which was barely distinguishable macroscopically from TRIVA cases.
* Corresponding author. Address: Department of Legal Medicine, School of Medicine, Tokyo Women’s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Tel.: +81 3 5269 7300; fax: +81 3 5269 7300. E-mail address: [email protected] (A. Ro). 1344-6223/$ - see front matter Ó 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.legalmed.2009.02.067
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A. Ro et al. / Legal Medicine 11 (2009) S66–S70 Table 1 Clinical summary and autopsy findings of four cases of TRIVA. Case
Age
Sex
Nature of trauma
Survival time
Ruptured IVAa
Other head injury
1 2 3 4
55 43 14 49
M M M M
Fist blows to the face Fist and umbrella blows to the face Fist blow to the neck Crushing of the body inside a car and impact on the road
3 days: unconscious immediately 6 days: unconscious immediately 28 days: unconscious immediately 2.5 h
Left Left Left Left Right
None None None Skull fracture
a
IVA, intracranial vertebral artery.
Fig. 1. Representative cases of TRIVA (a–c) and NIVAD (d–f). (a) Macroscopic appearance of TRIVA at the cerebral base after removal of superficial blood. (b) Macroscopic appearance of IVAs. Arrows indicate the ruptured site at bilateral IVAs. (c) Scheme of longitudinal rupture of TRIVA. (d) Macroscopic appearance of NIVAD at the cerebral base after removal of superficial blood. (e) Macroscopic appearance of IVAs. Arrow indicates ruptured site with fusiform aneurysm. (f) Scheme of longitudinal rupture of NIVAD.
3.2. Histopathological findings in the ruptured area The most specific histopathological characteristic that we found for differentiation between TRIVA and NIVAD cases was detected in the ruptured adventitia (Fig. 2). All TRIVA cases were transmural rupture without extension of the adventitia. On the other hand, extension of the adventitia was observed in all NIVAD cases. 3.3. Histopathological findings of the peripheral lesion of the rupture In TRIVA cases, an oblique tear of the intima and media was observed at the peripheral lesion of the rupture (Fig. 3). In contrast, in NIVAD cases, the intimal tear occurred at the recessed vascular wall according to massive medial defect. 3.4. Additional histopathological findings in non-ruptured lesions Several specific characteristics were detected for each of the following conditions. In TRIVA cases, the numbers of small incomplete tears of the intima or media were frequently observed without extension of the adventitia (Fig. 4a). Fragmentation of internal elastic lamina was also observed in TRIVA cases (Fig. 4b). In contrast, previous arterial dissections were sometimes detected in NIVAD cases (Fig. 4c). Medial degeneration or defects were observed in all NIVAD cases (Fig. 4d). These features were not always
observed; however, it usually confirmed as specific features of either case. Furthermore, these features were observed not only in ruptured IVAs but also in contralateral IVAs or other intracranial arteries.
4. Discussion Several different etiologies are believed to be involved in the case of SAH due to ruptured IVA: (1) traumatic rupture of the intact IVA by external force, (2) spontaneous rupture of an IVA aneurysm or dissection, (3) rupture of a latent IVA aneurysm or dissection by external force, and (4) delayed rupture of a traumatic intracranial aneurysm. In this report, we focused our investigation on the former two conditions. Isolated traumatic SAH is an infrequent consequence of fatal head injuries in approximately 3.4–11% cases in medicolegal autopsy [2,4]. Tatsuno and Lindenberg proposed several mechanisms for tearing of intracranial arteries: short duration oscillations of the brain, stretching force from hyperextension, and a momentary increase in intra-arterial pressure as a result of a blow to the carotid artery in the neck [8]. Isolated traumatic SAH is usually caused by a traumatic rupture of the IVA or in other posterior circulations [1–4]. TRIVA can occur by a small injury such as a single strike to the neck or head. TRIVA tends to cause diffuse basal
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Fig. 2. Histological characteristics of the ruptured site. Each of the histopathological photos of TRIVA and NIVAD cases are the same cases as shown in Fig. 1. Arrows indicate adventitia and arrowheads indicate intima of the ruptured site. (a) Scheme of the ruptured site of TRIVA. (b) Microscopic photo of the ruptured site of TRIVA (Elastica van Gieson stain). It was a transmural rupture without extension of the adventitia. (c) cheme of the ruptured site of NIVAD. (d) Microscopic photo of the ruptured site of NIVAD (Elastica van Gieson stain). The adventitia was widely extended by the medial dissecting hematoma.
Fig. 3. Histological characteristics of the peripheral lesion of the intimal tear. (a) Scheme of the peripheral lesion of TRIVA. (b) Microscopic photo of the peripheral lesion of TRIVA (Elastica van Gieson stain). It was an oblique tear of the intima and media. (c) Scheme of the peripheral lesion of NIVAD. (d) Microscopic photo of the peripheral lesion of NIVAD (Elastica van Gieson stain). The intimal tear occurred at the recessed vessel wall according to a massive medial defect.
SAH without serious skull fracture or brain contusion. Therefore, if postmortem head computer tomography was performed, it would show that the diffuse basal SAH is indistinguishable from TRIVA and NIVAD. Therefore, differential diagnosis between TRIVA and NIVAD still remains a medicolegal problem. Usually, TRIVA has been diagnosed by referring to circumstances before death, such as the existence of neck or head injury. However, we sometimes experience fatal NIVAD cases accompanied by consecutive head injury [9]. Otherwise, macroscopic appearance of longitudinal ruptures of IVA is considered as a characteristic of TRIVA [10]. However, longitudinal ruptures were de-
tected in both TRIVA and NIVAD cases in this study. Therefore, another method is required for differential diagnosis between TRIVA and NIVAD. In the current study, we attempted to establish histopathological identification between TRIVA and NIVAD (Table 2) [11,12]. The step-serial observations showed that the most specific characteristic for differentiation between TRIVA and NIVAD was the shape of the ruptured adventitia. Extension of the adventitia was clearly observed at the ruptured lesion in every NIVAD case. This finding suggests that there is a time lag between a medial dissecting hematoma and fatal rupture of the adventitia in NIVAD cases.
A. Ro et al. / Legal Medicine 11 (2009) S66–S70
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Fig. 4. Additional characteristic findings of non-ruptured areas. (a) Small incomplete tears of the intima and media (arrows) in a TRIVA case (Elastica van Gieson stain). (b) Fragmentized internal elastic lamina(arrow) in a TRIVA case (Elastica van Gieson stain). (c) Previous NIVAD (asterisk) in a NIVAD case (Elastica van Gieson stain). (d) Medial degeneration (arrows) in a NIVAD case (Elastica van Gieson stain). Table 2 Macroscopic and histopathological characteristics of TRIVA and NIVAD. TRIVAa
NIVADb
Longitudinal rupture
Fusiform aneurysm with longitudinal rupture
Transmural arterial rupture Not extended Oblique tear of the intima and media
Arterial dissection
Macroscopic appearance
Histopathological findings Ruptured site Appearance Adventitia Peripheral lesion Non-ruptured site Additional findings(not always present)
Small incomplete tears Fragmentized internal elastic lamina
a b
Extended Intimal tear according to medial defect Previous non-ruptured dissection Medial degeneration or defect
TRIVA, traumatic rupture of the intracranial vertebral artery. NIVAD, nontraumatic intracranial vertebral artery dissection.
In contrast, TRIVA showed a trilaminar transmural rupture, which occurred at the same time as the head injury. These specific features were confirmed in every TRIVA case. We propose that histopathological observation of the adventitia at a ruptured lesion is a novel differential viewpoint between TRIVA and NIVAD. Additionally, other specific characteristics for each condition were detected by histopathological examination. For TRIVA, small incomplete tears of the intima and media were frequently found in both ruptured and non-ruptured lesions. They formed oblique tears without extension of adventitia. The peripheral lesion of the rupture also appeared as oblique tears. In addition, as a result of multiple tears, a fragmentized internal elastic lamina was also observed in TRIVA cases. Fragmentation of the internal elastic lamina or small intimal damage of the intracranial artery have been proposed as additional histopathological findings of brain injury by some researchers [1,13,14]. These findings would be useful in the case of delayed fatal sequelae [15]. In our case, even one month later after IVA injury, oblique tears or fragmentized internal elastic
lamina were confirmed despite the effect of vascular repairing process. NIVAD usually occurs in middle aged men with hypertension [7,16]. It may cause recurrent dissections occurring in bilateral IVAs with spontaneous resolutions [7]. Previous NIVADs were confirmed as a repaired medial hematoma organized by collagen fibers accompanied by small tears of the internal elastic lamina. In this study, previous dissections were frequently confirmed at both ruptured and non-ruptured intracranial arteries in NIVAD cases. In addition, prodromal symptoms related to arterial dissections such as head or neck pain were often complained of before lethal attacks in NIVAD cases. Our previous study of 58 NIVAD cases revealed that previous IVA dissection was detected in 43% and that prodromal symptoms related to IVA dissections were detected in 43%[16].Such clinical symptoms prior to death might be helpful for diagnosis as NIVAD. With regard to other histopathological characteristics of NIVAD, medial degenerations or defects were detected in all NIVAD cases in this study. In addition, the peripheral lesion of the rupture appeared as intimal tears at the recessed vascular wall caused by a massive medial defect. It is believed that medial degenerations or defects result in the pathogenesis of NIVAD [9,12,17,18].The pathogenesis of NIVAD remains unclear. Further investigation is required to determine the role that medial lesions play in the mechanism of NIVAD. Finally, we would like to emphasize the importance of histopathological examination of intracranial arteries for differentiation between TRIVA and NIVAD in medicolegal autopsy cases of ruptured vertebral arteries. The reference of circumstance before death such as an existence of head injury or prodromal symptom is important but obscure for objective differentiation. Furthermore, it is very difficult to differentiate between TRIVA and NIVAD by macroscopic findings. Histopathological characteristics such as those described in this paper could offer objective differentiation among the two alternative conditions. Investigations using stepserial sections are also desirable for reliable observation [14] because medial defects or small incomplete tears resemble technical artifacts. Additionally, other histopathological characteristics of both TRIVA and NIVAD were detected at non-ruptured areas in the intracranial artery. Histopathological investigation of not only
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ruptured sites but also of non-ruptured cerebral arteries is strongly recommended. In conclusion, histopathological investigation using step-serial sections is a reliable method for differential diagnosis between traumatic rupture and nontraumatic intracranial artery dissections occurring at the IVA resulting in fatal SAH. The most striking histopathological feature was adventitial extension at the ruptured site in nontraumatic cases. Additional histopathological characteristics for each pathogenesis were confirmed not only in ruptured IVAs but also in non-ruptured IVAs. These morphological differentiations could be valuable for medicolegal diagnosis in cases of SAH due to a ruptured IVA. Conflict of interest This study was supported in part by the Grant-in-Aid for Scientific Research for Young Scientists to Ayako Ro, M.D., Ph.D(19790448). The funding source had no involvement in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. References [1] Dowling G, Curry B. Traumatic basal subarachnoid hemorrhage report of six cases and review of the literature. Am J Forensic Med Pathol 1988;9:23–31. [2] Okada Y, Mukaida M, Mori A, Tanabe R, Ishiyama I. Isolated traumatic subarachnoid hemorrhage. Jpn J Traumatol Occup Med 1989;37:279–85. [3] Bunai Y, Nagai A, Nakamura I I, Ohya I. Traumatic rupture of the basilar artery: report of two cases and review of the literature. Am J Forensic Med Pathol 2000;21:343–8. [4] Hiraiwa K, Sato T, Sasaki T, Mizusawa I, Nata M, Kodama N. Medico-legal aspects of traumatic injury of the vertebrobasilar artery. Neurol Med Chir (Tokyo) 2005;45:549–55. [5] Murai T, Baba M, Ro A, Murai N, Matsuo Y, Takada A, et al. Sudden death due to cardiovascular disorders: a review of the studies on the medico-legal cases in Tokyo. Keio J Med 2001;50:175–81.
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