Forensic
Science International,
Elsevier Scientific Publishers
53 (1992) 69 - 79 Ireland Ltd.
THYMUS OF ABUSED/NEGLECTED
69
CHILDREN
TATSUSHIGE FUKUNAGAqb*, YASUHIKO MIZOIb~e, AKIRA YAMASHITAd, MITSUKO YAMADA’, YOSHIO YAMAMOTOB, YOSHITSUGU TATSUNOb+ and KATSUJI NISHIa aDepartment of Legal Medicine, Shiga University of Medical Science, Ohtsu 520-21,
bMedical Exam-
iner’s Office of Hyogo Prefecture, Kobe 650, cDepartment of Legal Medicine, Osaka Medical College, University School of Medicine, Takatsuki 569, dThe 2nd Department of Anutomy, Hamamatsu Hamamatsu 491-31 and eDepartment of Legal Medicine, Kobe University School of Mediciw, Kobe 650 (Japan)
(Received October 22nd, 1991) (Revision received December 8th, 1991) (Accepted December 26th, 1991)
Summary Forty-six cases of child abuselneglect autopsied during the period of 1967 to 1990 were investigated. The weight and histological findings of the thymus were compared with those of control children. In most abused and/or neglected children, the weight of the thymus decreased conspicuously. Involution correlated wel1 to the degree and period of maltreatment. In cases without weight loss of the thymus, i.e. spasmodic abuse by a mentally deranged parent or foster parent, a short history of maltreatment was noted. On the other hand, marked involution was observed in cases of prolonged physical abuse and/or neglect. Microscopically, a decrease in the number and pyknosis of lymphocytes were observed in the involuted thymus. Atrophy of the thymus was more conspicuous in the cortex than in medulla. Immunohistochemically, CD-la positive cells (immature thymocytes) decreased in cases with thymic involution. This involution appears to be an important index of the degree and duration of child abuse/neglect. Furthermore, thymic involution in the early stage of childhood may also be related to insufficiency of the immune system. Key words: Child abuse; Child neglect;
Thymus gland; Thymic involution; Stress; T lymphocytes;
Immunohistochemistry
Introduction Child abuse/neglect is a crucial issue of public concern, gaining wide attention among paediatricians, psychiatrists, social workers, forensic pathologists, and others. In the United States, approximately 1% of al1 children per year are documented as being victims of abuse. Substantiated cases of physical abuse Corres-pondonce to: T. Fukunaga, Department of Legal Medicine, Shiga University of Medical Science, Sets Tsukinowa-cho, Ohtsu 520-21, Japan. *Present address: Biomedical Research Center, ALK0 Ltd., POB 350, SF-00101 Helsinki, Finland. 0379-0738/92/$05.00
0 1992 Elsevier Scientific Publishers Printed and Published in Ireland
Ireland Ltd.
70
point to a startling figure of 1200 per. million population per year [ll. In Japan, child abuse/neglect has increased and fatalities have risen as a result. Since Kempe first coined the phrase ‘battered child syndrome’ in 1962 [2], varied forms of maltreatment have been identified, such as physical abuse, neglect, sexual abuse, poisoning, Munchausen syndrome by proxy, etc. In medico-legal autopsies, it is often difficult to decide whether the injuries, malnutritional states and causes of death are due to maltreatment or not. In the present study, attention was focused on the effect of child abuselneglect on thymic involution as an index of stress. Materials and Methods Forty-six cases of child abuse andlor neglect were autopsied in the Department of Legal Medicine, Kobe University School of Medicine (43 cases), Shiga University of Medical Science (two cases), and the Medical Examiner’s Office of Hyogo Prefecture (one case) during the period of 1967 to 1990. The weight and histological findings of the thymus were compared with a control pool of 349 children autopsied in the Medical Examiner’s Office of Hyogo Prefecture and Kobe University. The control children comprised victims of infanticides, traffic accidents and homicide, without any history of abuse. Cases with histories of longterm medical treatment and thymic neoplasma, endocrine diseases, or other anomalies were excluded from the control. The degrees of physical abuse were divided into the following four stages: generally injuries, more than 50% of whole body surface (+ + +); regional injuries, e.g. only on the head or face (+); intermediate stage between the former two stages (+ +); no physical injuries (-). The durations of abuse/neglect were estimated based on postmortem findings and police reports. Blocks of thymus were immediately frozen in dry ice and stored at - 70°C. The sections were cut on a cryostat to 10 Pm thickness, and were fixed in cold acetone for 10 min. Immunohistochemical staining for T cells were done using monoclonal antibodies in combination with the avidin-biotin-peroxidase complex (ABC) method [3]. The reagents used were commercially supplied as follows: Becton Dickinson Monoclonal Center Inc. (anti-CDla = Leu-6, antiCD3 = Leud, anti-CD4 = Leu-3a, and anti-CD8 = Leu-Ba monoclonal antibodies), Vector Laboratories Inc. (biotinated second antibody and ABC complex). Results An outline of the forty-six cases of child abuselneglect pooled in this study is summarized in Table 1. Figure 1 shows the relationship between age and weight of the thymus, and the ratio of thymuslbody weight. The relations between age and height, body weight, and other organs are shown in Fig. 2. In several cases, a delay of the development is shown. In most abused andlor neglected children, a conspicuous decrease in the weight of the thymus was noted, and the ratio of the thymus/body weight was also markedly lower than that of control children.
F
F
M
M
3.7
5.2
5.9
9.0
10.0
10.0
4.7
5.2
7
8
9
10
11
12
13
14
SAH
F
3.0
6
1
Brain swelling Malnutrition
F
1.1
5
F
F
F
F
M
73
58
65
62
58
51
62
58
58
SD
SD. SAH 76.5
65
Strangulation 71 by hands SD 66
SAH
SD
Asphyxia
SD
3.7
M
4
Heat exhaustion SkuIl fracture Asphyxia
km)
death
3.0
M
M
Height
Cause of
3
1.4
month
sex
3.0
0
year
-Qe
2
1
No. Thymus
8
5
7
8
11
3.9
6.1
4.1
3.4
14.6
29
29.2
5.5
31.8
16.2
6.5
4.9 5.8
9.8
26.6
2.8
(g)
6
6
4.1
2.95
(kg)
Weight
Mother 31 Foster father 31 Mother 28 Stepmother 25 Mother 27 Father 29 Mother 27 Mother 37 Mother 23 Mother 25 Mother 25 Mother 21 Mother 27 Mother 22
Age fy.0.)
Assailants
Postpartum neurosis Postpartum neurosis Schizophenia
Schizophrenia
+
+
Psychosis
++ +++
6m
++
+
+
+
f
+
+
+
+
+
+
Degree of injury
ca. 1 y
2.5 m
Spasmodic
Spasmodic
5m
Spasmodic
3m
2 -3m
lm
3m
Spasmodic
Spasmodic
Spasmodic
Duratiím
SD: Subdural hematoma, SAH: Subrachnoidal hemorrhage, ED: EpiduraI hemataoma. M: male, F: female, y: year(s), m: month(s).
OUTLINES OF 46 ABUSED/NEGLECTED CASES
TABLE 1
2
31.8
11
80
Thymus
ll.2 23.7 20.7
18.2 28.3
6.6 13 14 9 ll.4 13
13 13.9 11 13
73.5 84 89 90 81 89 76 90 91 92 92
Malnutrition Brain swelling Cerebral contusion SD SD, SAH SAH Bronchial pneumonitis SD SD SD SD
F
F
M
M
M
F
F
F
F
M
M
M
11.0
ll.3
3.9
5.0
6.2
1.1
7.0
7.9
ll.7
0.0
0.8
2.3
19
20
21
22
23
24
25
26
27
29
30
28
18.8
8.6
78
ED, SD
F
8.0
18
3
7.2
4
8
73
Chronic SD
F
6.6
17
2
15.5
9
80
SD
F
0.0
16
35
3
3.8
53.3
0.7
4.1
13
7.6
72
Brain swelling SD
(g)
(cml
a!eath
Weight (kg)
Height
Cause of
M
month
Sex
6.0
year
Age
15
No.
TABLE 1 (continued)
Father 43 Mother 22 Stepfather 27 Mother 31 Acquaintance 54 Mother, 22 Grandmother, Mother 25 Mother 36 Grandmother. Father, 29 Father 21 Mother 37 Mother 23 Mother 29 Foster father 27 Father 26 Mother 29
Age (Y.o.)
Assailants
55
45
Neurosis
Neurosis
Mentally retarded Schizophrenia
Psychosis
+ +
4m 3-
+ ++
3m ?
4m
+
+
++
+++
+
+
> 1Y
Spasmodic
3m
3m
Spasmodic
Spasmodic
ca. 1 y
++
++
3m
2m
++
++
+
Degree of injury
2m
2-3m
Spasmodic
Duration
w
F
F
10.0
0.2
45
46
6
17
17.4
F
6.1
44
23
14.4
M
6.0
43
23.9
6
15.9
SD
102
tr
9.5
105
Cerebral 106 contusion Malnutrition 101
Asphyxia
116
SAH, SD
21
M
6.0
42
6.6
98
Shock
17
M
5.1
5
41
28.2
14
96
Shock
M
7.5
40
22
15
96
Asphyxia
M
3.0
39
29
103
SD
M
0.0
38
9 20.5
104
SD
M
0.0
4
37
4.2
8.3
78
SD
F
5.0
36
5
15.2
103
M
8.6
35
35
12.6
92
copoisoning SAH
M
7.0
34
4.9
12
95
Mah-mtrition
M
4.1
33
18.5
14
94
SD
M
2.7
32
7.9
15.8
90
SD
M
2.4
31
Stepfather 30 Uncle 26 Father 32 Mother 31 Stepmother 20 Father 32 Stepmother 34 Stepmother 25 Stepfather 31 Father-in-law, 27 Mother, 25 Father 30 Stepmother 31 Mother 30 Stepfather Schizophrenia 36 Mother 34 Mother 25
++ ti tt
4m lm Spasmodic
>2Y
+++
ti+
7m
6m
ttt
tt
lm
Spasmodic
fff
6m
t
ttt
l-2y
Spasmodic
tt
ttt
ti
ti+
3.5 m
Spasmodic
3m
lm
4-5 m
o
:ï 1,
A
LAP .
0
o-012 ’
&AA I
h t
1
2
A AAA
1
I
4
3
A*.b
A I
A
AAAhAA h I
5
I
6
A
A
I
7
I
8
1
9
I
3
I
4
I
5
10yrS
A h
t
1
I
6
I
7
I
8
I
910
l
YS
Fig. 1. Weight of the thymus (g) and the ratio of thymus (g)/body weight (kg). Circles and bars show means * S.D. of control children. Open and closed triangles indicate femaleand male, respectively.
Involution was correlated with the degree and period of physical abuse and neglect, as shown in Fig. 3. NO weight loss of the thymus was observed in cases with a short history of battery, i.e. spasmodic or short-period abuse by a mentally deranged parent or foster parent. On the other hand, marked involution was observed in cases of child neglect without injuries, as wel1 as in cases of physical abuse. Weight loss of the spleen and other organs in most cases was not significantly different compared with control children.
o-a’ 8 r b ’ 8 8 ’ c g 0123456789lOyrS
0123456789IoyrS~""""""
o
1 2
3
4
5
6
7
a
9
loyrs
0
1
3
4
5
6
7
8
9
1OyrS
2
Fig. 2. The height and body weight [al, the weight (g) and the ratio to body weight (kg) of the heart [bl, liver [c] and spleen [dl. Marks are the same as Fig. 1.
Microscopically, a decrease in the number of lymphocytes in the thymus and lymphocyte pyknosis were observed in cases of thymic involution. In particular, thymic atrophy was more marked in the cortex than in the medulla. In cases with marked thymic involution, a thickening of the capsule and lipid depletion in the zona fasciculata and reticulata were found in the adrenal gland. The spleen from
P
Fig. 3. The degree of thymic involution and the period of child abuselneglect. (+ + +)-(-): The degree of physical injuries on the body surface is mentioned in Materials and Methods. Open and closed triangles indicate female and male, respectively.
these cases showed atrophy of the follicles and periarterial lymphoid sheath. In the lymph nodes, atrophy of the follicles and paracortical areas were also observed. In an immunohistochemical examination of the thymus in case No. 41, CDla positive cells (immature thymocytes) and CD8 positive cells (cytotoxiclsuppressor T lymphocytes) were conspicuously decreased in cases of thymic involution. CD4 positive cells (helperlinducer T lymphocytes) also decreased in number with a total decrease of CD3 positive cells (pan T lymphocytes), as shown in Fig. 4. In most of these cases, a delay in healing of injury was often found. Particularly in case No. 41, excoriation and laceration showed drying of the surfaces, but no granulomatous change in connective tissue. Histologically, the inflammatory responses, i.e. infntration of white cells and proliferative changes of connective tissue were not found around the injuries. Discussion According to Selye’s stress theory [4], the thymus is the organ most sensitive
Fig. 4. Immunohistochemical findings of the thymus in case No. 41 using anti-CDla [bl, anti-CD4 [c] and anti-CD8 [d] monoclonal antibodies as primary antibodies.
[al, anti-CD3
78
to stress. In the present study, examinations were carried out on thymic involution of abused/neglected children. Whereas reports on thymic involution [5,6] or immunological states 16,71 of abused/neglected children are scarce, the modes of abuse, mechanism of injuries, and circumstances of abused children have often been reported in many papers and reviews. Many kinds of stress exert immunosuppressive effects, principally mediated by the nervous and endocrine systems, through substances such as corticosteroids, endorphin, etc. [8]. Its mechanism of action is, however, not yet completely elucidated. In the present study of 46 abusedlneglected children, severe stress caused weight loss of the thymus and pathology of the thymus and adrenal gland. Furthermore, the degree of thymic involution correlated wel1 to the period of abuse and neglect. Therefore, stress to children could wel1 be reflected in weight loss and thymic involution. Indeed, thymic involution occurs physiologically not only after puberty, but also with steroid treatments, chemotherapy, radiation, etc. Since physiological involution seldom occurs in early childhood, thymic involution could thus be one important index of child abuse/neglect. Copeland reported that panhypogammaglobulinemia could masquerade as child abuse [5]. In his report, a 15-month-old boy showed relatively lower levels of both immunoglobulins and complements, and a markedly involuted thymus weighing 7.7 g. It remains debatable whether hypogammaglobulinemia was due to congenital immunoinsufficiency or child abuse [9]. Our present data revealed that the involuted thymus in this case could be due to long-term stress. Furthermore, the boy’s infectieus states might be related to child abuse. Serum levels of globulins do not always reflect the immune state, because malnutrition may also result in low levels of immunoglobulins and complements, as wel1 as serum protein. Therefore, his hypogammaglobulinemia could be caused by long-term stress. Lowering of T cel1 function owing to thymic involution should not only be related to cell-mediated immune system, but more to the humoral immune system. If the immunodeficient states were due to long-term abuse, the cause of death should be due to infectieus disease caused by child abuse, i.e. homicide. Neonatally-thymectomized animals show atrophy of lymphoid tissues, and lowering of cellular response [8]. Marked involution in early childhood may be similar to partial thymectomy, and therefore, child abuselneglect might lead to immunoinsufficiency. Histological findings of abusedlneglected children with marked thymic involution showed atrophies in the T-cel1 zones of the lymph nodes and spleen. Moreover, the B-cel1 zones also showed atrophy in these cases. Immunohistochemically, immature thymocytes and functionally mature T lymphocytes decreased in the thymus. These findings indicate that immune states were suppressed not only in cell-mediated reactions but also in humoral antibody reactions. It can be said that immunosuppression is caused by a severe long-term stress on children. The delay in healing of injuries might also be caused by the immunoinsufficiency. Several cases of child abuse with severe polymicrobial infection have been reported [10 - 151, in which most of these infections were intentionally produced by their mother. Forensic pathologists should take into account the physiological and functional changes in abused/neglected children, especially when the cause-
79
of-death was due to infections, e.g. pneumonia, bronchitis, sepsis, etc. But, accurate diagnosis may be difficult since offenders of child abuse seldom tel1 the truth. It is often even difficult to estimate whether physical injuries are intentional or brought on by accident. One important problem in deciding the cause of death is whether the infectieus state was due to child abuselneglect or not. From a medicolegal point of view, victims of child abuselneglect also should not only be protected by the law, but also be regularly examined as to their immune and hormonal states. In conclusion, child abuse/neglect causes thymic involution, which leads to a lowering of immune states. Thymic involution represents an important finding in the estimation of the degree and duration of child abuselneglect. Acknowledgements This study was supported in part by Grant-in-Aid for Encouragement of Young Scientists of the Japanese Ministry of Education, Science and Culture in 1990 (02857095) and in 1991 (03857084). We would like to thank Ms. Kanako Nakagawa (Kobe University) and Mr. Yuuichi Hattori (Hamamatsu University) for their technical assistance. References
8 9 10 11 12 13 14 15
B.D. Schmitt, The child with nonaccidental trauma. In R.E. Helfer and R.S. Kempe (eds.), 2% Buttered Child, 4th ed., The University of Chicago Press, Chicago, 1987, pp. 178- 196. C.H. Kempe, F.N. Silverman, B.F. Steele, W. Droegemueller and H.K. Silver, The batteredchild syndrome. J. Am. Med. Assoc., 17 (1962) 17-24. S.M. Hsu, L. Raine and H. Franger, Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J. Histocha. Qtoch., 29 (1981) 577 - 580. H. Selye, Stress, Acts Inc. Medical Publishers, Montreal, 1950, pp. 452 - 448. A.R. Copeland, A case of panhypogammaglobulinemia masquerading as child abuse. J. Fortmsic Sci., 33 (1988) 1493- 1496. P.L. Morrow, Caffeine toxicity: A case of child abuse by drug ingestion. J. Forensic Sci., 32 (1987) 1801- 1805. S. Kohl, L.K. Pickering and E. Dupree, Child abuse presenting as immunodeficiency disease. J. Pediutr., 93 (1978) 466 - 468. I.M. Roitt, J. Brostoff and D.K. Male, Zmmunology, 2nd ed., Gower Medical Publishing, London, New York, 1989. T. Fukunaga, Discussion of “a case of panhypogammaglobulinemia masquerading as child abuse” with regard to the involution of thymus. J. Forensic Sci., 35 (1990) 232-234. C. Koch and N. Hfiiby, Severe child abuse presenting as polymicrobial bacteremia. Acta Paediatr. Stand., 77 (1988) 940-943. N.A. Halsley, J.M. Frentz, T.W. Tucker, T. Sproles, J. Redding and R.S. Daum, Recurrent nosocomial polymicrobial sepsis secondary child abuse. Lancet, ii (1983) 558 - 560. Y. Zohal, G. Avidan, Y. Shvili and N. Laurian, Otolaryngologic cases of Munchausen’s syndrome. Luryngoscope, 97 (1987) 201-203. T.E. Liston, P.L. Levine and C. Anderson, Polymicrobial bacteremia due to Polle syndrome: The child abuse variant of Munchausen syndrome by proxy. Pediutr., 72 (1983) 211-213. A.J. Palmer and G.J. Yoshimura, Munchausen syndrome by proxy. J. Am. Acad. Child Psychiutry, 23 (1984) 503-508. D. Hodge, 111, W. Schwartz, J. Sargent, J. Bodurtha and S. Starr, The bacteriologically battered baby: another case of Munchausen by proxy. Ann. Emerg. Med., 11 (1982) 205-207.
Science International,
Elsevier Scientific Publishers
53 (1992) 69 - 79 Ireland Ltd.
THYMUS OF ABUSED/NEGLECTED
69
CHILDREN
TATSUSHIGE FUKUNAGAqb*, YASUHIKO MIZOIb~e, AKIRA YAMASHITAd, MITSUKO YAMADA’, YOSHIO YAMAMOTOB, YOSHITSUGU TATSUNOb+ and KATSUJI NISHIa aDepartment of Legal Medicine, Shiga University of Medical Science, Ohtsu 520-21,
bMedical Exam-
iner’s Office of Hyogo Prefecture, Kobe 650, cDepartment of Legal Medicine, Osaka Medical College, University School of Medicine, Takatsuki 569, dThe 2nd Department of Anutomy, Hamamatsu Hamamatsu 491-31 and eDepartment of Legal Medicine, Kobe University School of Mediciw, Kobe 650 (Japan)
(Received October 22nd, 1991) (Revision received December 8th, 1991) (Accepted December 26th, 1991)
Summary Forty-six cases of child abuselneglect autopsied during the period of 1967 to 1990 were investigated. The weight and histological findings of the thymus were compared with those of control children. In most abused and/or neglected children, the weight of the thymus decreased conspicuously. Involution correlated wel1 to the degree and period of maltreatment. In cases without weight loss of the thymus, i.e. spasmodic abuse by a mentally deranged parent or foster parent, a short history of maltreatment was noted. On the other hand, marked involution was observed in cases of prolonged physical abuse and/or neglect. Microscopically, a decrease in the number and pyknosis of lymphocytes were observed in the involuted thymus. Atrophy of the thymus was more conspicuous in the cortex than in medulla. Immunohistochemically, CD-la positive cells (immature thymocytes) decreased in cases with thymic involution. This involution appears to be an important index of the degree and duration of child abuse/neglect. Furthermore, thymic involution in the early stage of childhood may also be related to insufficiency of the immune system. Key words: Child abuse; Child neglect;
Thymus gland; Thymic involution; Stress; T lymphocytes;
Immunohistochemistry
Introduction Child abuse/neglect is a crucial issue of public concern, gaining wide attention among paediatricians, psychiatrists, social workers, forensic pathologists, and others. In the United States, approximately 1% of al1 children per year are documented as being victims of abuse. Substantiated cases of physical abuse Corres-pondonce to: T. Fukunaga, Department of Legal Medicine, Shiga University of Medical Science, Sets Tsukinowa-cho, Ohtsu 520-21, Japan. *Present address: Biomedical Research Center, ALK0 Ltd., POB 350, SF-00101 Helsinki, Finland. 0379-0738/92/$05.00
0 1992 Elsevier Scientific Publishers Printed and Published in Ireland
Ireland Ltd.
70
point to a startling figure of 1200 per. million population per year [ll. In Japan, child abuse/neglect has increased and fatalities have risen as a result. Since Kempe first coined the phrase ‘battered child syndrome’ in 1962 [2], varied forms of maltreatment have been identified, such as physical abuse, neglect, sexual abuse, poisoning, Munchausen syndrome by proxy, etc. In medico-legal autopsies, it is often difficult to decide whether the injuries, malnutritional states and causes of death are due to maltreatment or not. In the present study, attention was focused on the effect of child abuselneglect on thymic involution as an index of stress. Materials and Methods Forty-six cases of child abuse andlor neglect were autopsied in the Department of Legal Medicine, Kobe University School of Medicine (43 cases), Shiga University of Medical Science (two cases), and the Medical Examiner’s Office of Hyogo Prefecture (one case) during the period of 1967 to 1990. The weight and histological findings of the thymus were compared with a control pool of 349 children autopsied in the Medical Examiner’s Office of Hyogo Prefecture and Kobe University. The control children comprised victims of infanticides, traffic accidents and homicide, without any history of abuse. Cases with histories of longterm medical treatment and thymic neoplasma, endocrine diseases, or other anomalies were excluded from the control. The degrees of physical abuse were divided into the following four stages: generally injuries, more than 50% of whole body surface (+ + +); regional injuries, e.g. only on the head or face (+); intermediate stage between the former two stages (+ +); no physical injuries (-). The durations of abuse/neglect were estimated based on postmortem findings and police reports. Blocks of thymus were immediately frozen in dry ice and stored at - 70°C. The sections were cut on a cryostat to 10 Pm thickness, and were fixed in cold acetone for 10 min. Immunohistochemical staining for T cells were done using monoclonal antibodies in combination with the avidin-biotin-peroxidase complex (ABC) method [3]. The reagents used were commercially supplied as follows: Becton Dickinson Monoclonal Center Inc. (anti-CDla = Leu-6, antiCD3 = Leud, anti-CD4 = Leu-3a, and anti-CD8 = Leu-Ba monoclonal antibodies), Vector Laboratories Inc. (biotinated second antibody and ABC complex). Results An outline of the forty-six cases of child abuselneglect pooled in this study is summarized in Table 1. Figure 1 shows the relationship between age and weight of the thymus, and the ratio of thymuslbody weight. The relations between age and height, body weight, and other organs are shown in Fig. 2. In several cases, a delay of the development is shown. In most abused andlor neglected children, a conspicuous decrease in the weight of the thymus was noted, and the ratio of the thymus/body weight was also markedly lower than that of control children.
F
F
M
M
3.7
5.2
5.9
9.0
10.0
10.0
4.7
5.2
7
8
9
10
11
12
13
14
SAH
F
3.0
6
1
Brain swelling Malnutrition
F
1.1
5
F
F
F
F
M
73
58
65
62
58
51
62
58
58
SD
SD. SAH 76.5
65
Strangulation 71 by hands SD 66
SAH
SD
Asphyxia
SD
3.7
M
4
Heat exhaustion SkuIl fracture Asphyxia
km)
death
3.0
M
M
Height
Cause of
3
1.4
month
sex
3.0
0
year
-Qe
2
1
No. Thymus
8
5
7
8
11
3.9
6.1
4.1
3.4
14.6
29
29.2
5.5
31.8
16.2
6.5
4.9 5.8
9.8
26.6
2.8
(g)
6
6
4.1
2.95
(kg)
Weight
Mother 31 Foster father 31 Mother 28 Stepmother 25 Mother 27 Father 29 Mother 27 Mother 37 Mother 23 Mother 25 Mother 25 Mother 21 Mother 27 Mother 22
Age fy.0.)
Assailants
Postpartum neurosis Postpartum neurosis Schizophenia
Schizophrenia
+
+
Psychosis
++ +++
6m
++
+
+
+
f
+
+
+
+
+
+
Degree of injury
ca. 1 y
2.5 m
Spasmodic
Spasmodic
5m
Spasmodic
3m
2 -3m
lm
3m
Spasmodic
Spasmodic
Spasmodic
Duratiím
SD: Subdural hematoma, SAH: Subrachnoidal hemorrhage, ED: EpiduraI hemataoma. M: male, F: female, y: year(s), m: month(s).
OUTLINES OF 46 ABUSED/NEGLECTED CASES
TABLE 1
2
31.8
11
80
Thymus
ll.2 23.7 20.7
18.2 28.3
6.6 13 14 9 ll.4 13
13 13.9 11 13
73.5 84 89 90 81 89 76 90 91 92 92
Malnutrition Brain swelling Cerebral contusion SD SD, SAH SAH Bronchial pneumonitis SD SD SD SD
F
F
M
M
M
F
F
F
F
M
M
M
11.0
ll.3
3.9
5.0
6.2
1.1
7.0
7.9
ll.7
0.0
0.8
2.3
19
20
21
22
23
24
25
26
27
29
30
28
18.8
8.6
78
ED, SD
F
8.0
18
3
7.2
4
8
73
Chronic SD
F
6.6
17
2
15.5
9
80
SD
F
0.0
16
35
3
3.8
53.3
0.7
4.1
13
7.6
72
Brain swelling SD
(g)
(cml
a!eath
Weight (kg)
Height
Cause of
M
month
Sex
6.0
year
Age
15
No.
TABLE 1 (continued)
Father 43 Mother 22 Stepfather 27 Mother 31 Acquaintance 54 Mother, 22 Grandmother, Mother 25 Mother 36 Grandmother. Father, 29 Father 21 Mother 37 Mother 23 Mother 29 Foster father 27 Father 26 Mother 29
Age (Y.o.)
Assailants
55
45
Neurosis
Neurosis
Mentally retarded Schizophrenia
Psychosis
+ +
4m 3-
+ ++
3m ?
4m
+
+
++
+++
+
+
> 1Y
Spasmodic
3m
3m
Spasmodic
Spasmodic
ca. 1 y
++
++
3m
2m
++
++
+
Degree of injury
2m
2-3m
Spasmodic
Duration
w
F
F
10.0
0.2
45
46
6
17
17.4
F
6.1
44
23
14.4
M
6.0
43
23.9
6
15.9
SD
102
tr
9.5
105
Cerebral 106 contusion Malnutrition 101
Asphyxia
116
SAH, SD
21
M
6.0
42
6.6
98
Shock
17
M
5.1
5
41
28.2
14
96
Shock
M
7.5
40
22
15
96
Asphyxia
M
3.0
39
29
103
SD
M
0.0
38
9 20.5
104
SD
M
0.0
4
37
4.2
8.3
78
SD
F
5.0
36
5
15.2
103
M
8.6
35
35
12.6
92
copoisoning SAH
M
7.0
34
4.9
12
95
Mah-mtrition
M
4.1
33
18.5
14
94
SD
M
2.7
32
7.9
15.8
90
SD
M
2.4
31
Stepfather 30 Uncle 26 Father 32 Mother 31 Stepmother 20 Father 32 Stepmother 34 Stepmother 25 Stepfather 31 Father-in-law, 27 Mother, 25 Father 30 Stepmother 31 Mother 30 Stepfather Schizophrenia 36 Mother 34 Mother 25
++ ti tt
4m lm Spasmodic
>2Y
+++
ti+
7m
6m
ttt
tt
lm
Spasmodic
fff
6m
t
ttt
l-2y
Spasmodic
tt
ttt
ti
ti+
3.5 m
Spasmodic
3m
lm
4-5 m
o
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9
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3
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4
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5
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6
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7
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910
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YS
Fig. 1. Weight of the thymus (g) and the ratio of thymus (g)/body weight (kg). Circles and bars show means * S.D. of control children. Open and closed triangles indicate femaleand male, respectively.
Involution was correlated with the degree and period of physical abuse and neglect, as shown in Fig. 3. NO weight loss of the thymus was observed in cases with a short history of battery, i.e. spasmodic or short-period abuse by a mentally deranged parent or foster parent. On the other hand, marked involution was observed in cases of child neglect without injuries, as wel1 as in cases of physical abuse. Weight loss of the spleen and other organs in most cases was not significantly different compared with control children.
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o
1 2
3
4
5
6
7
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1
3
4
5
6
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2
Fig. 2. The height and body weight [al, the weight (g) and the ratio to body weight (kg) of the heart [bl, liver [c] and spleen [dl. Marks are the same as Fig. 1.
Microscopically, a decrease in the number of lymphocytes in the thymus and lymphocyte pyknosis were observed in cases of thymic involution. In particular, thymic atrophy was more marked in the cortex than in the medulla. In cases with marked thymic involution, a thickening of the capsule and lipid depletion in the zona fasciculata and reticulata were found in the adrenal gland. The spleen from
P
Fig. 3. The degree of thymic involution and the period of child abuselneglect. (+ + +)-(-): The degree of physical injuries on the body surface is mentioned in Materials and Methods. Open and closed triangles indicate female and male, respectively.
these cases showed atrophy of the follicles and periarterial lymphoid sheath. In the lymph nodes, atrophy of the follicles and paracortical areas were also observed. In an immunohistochemical examination of the thymus in case No. 41, CDla positive cells (immature thymocytes) and CD8 positive cells (cytotoxiclsuppressor T lymphocytes) were conspicuously decreased in cases of thymic involution. CD4 positive cells (helperlinducer T lymphocytes) also decreased in number with a total decrease of CD3 positive cells (pan T lymphocytes), as shown in Fig. 4. In most of these cases, a delay in healing of injury was often found. Particularly in case No. 41, excoriation and laceration showed drying of the surfaces, but no granulomatous change in connective tissue. Histologically, the inflammatory responses, i.e. infntration of white cells and proliferative changes of connective tissue were not found around the injuries. Discussion According to Selye’s stress theory [4], the thymus is the organ most sensitive
Fig. 4. Immunohistochemical findings of the thymus in case No. 41 using anti-CDla [bl, anti-CD4 [c] and anti-CD8 [d] monoclonal antibodies as primary antibodies.
[al, anti-CD3
78
to stress. In the present study, examinations were carried out on thymic involution of abused/neglected children. Whereas reports on thymic involution [5,6] or immunological states 16,71 of abused/neglected children are scarce, the modes of abuse, mechanism of injuries, and circumstances of abused children have often been reported in many papers and reviews. Many kinds of stress exert immunosuppressive effects, principally mediated by the nervous and endocrine systems, through substances such as corticosteroids, endorphin, etc. [8]. Its mechanism of action is, however, not yet completely elucidated. In the present study of 46 abusedlneglected children, severe stress caused weight loss of the thymus and pathology of the thymus and adrenal gland. Furthermore, the degree of thymic involution correlated wel1 to the period of abuse and neglect. Therefore, stress to children could wel1 be reflected in weight loss and thymic involution. Indeed, thymic involution occurs physiologically not only after puberty, but also with steroid treatments, chemotherapy, radiation, etc. Since physiological involution seldom occurs in early childhood, thymic involution could thus be one important index of child abuse/neglect. Copeland reported that panhypogammaglobulinemia could masquerade as child abuse [5]. In his report, a 15-month-old boy showed relatively lower levels of both immunoglobulins and complements, and a markedly involuted thymus weighing 7.7 g. It remains debatable whether hypogammaglobulinemia was due to congenital immunoinsufficiency or child abuse [9]. Our present data revealed that the involuted thymus in this case could be due to long-term stress. Furthermore, the boy’s infectieus states might be related to child abuse. Serum levels of globulins do not always reflect the immune state, because malnutrition may also result in low levels of immunoglobulins and complements, as wel1 as serum protein. Therefore, his hypogammaglobulinemia could be caused by long-term stress. Lowering of T cel1 function owing to thymic involution should not only be related to cell-mediated immune system, but more to the humoral immune system. If the immunodeficient states were due to long-term abuse, the cause of death should be due to infectieus disease caused by child abuse, i.e. homicide. Neonatally-thymectomized animals show atrophy of lymphoid tissues, and lowering of cellular response [8]. Marked involution in early childhood may be similar to partial thymectomy, and therefore, child abuselneglect might lead to immunoinsufficiency. Histological findings of abusedlneglected children with marked thymic involution showed atrophies in the T-cel1 zones of the lymph nodes and spleen. Moreover, the B-cel1 zones also showed atrophy in these cases. Immunohistochemically, immature thymocytes and functionally mature T lymphocytes decreased in the thymus. These findings indicate that immune states were suppressed not only in cell-mediated reactions but also in humoral antibody reactions. It can be said that immunosuppression is caused by a severe long-term stress on children. The delay in healing of injuries might also be caused by the immunoinsufficiency. Several cases of child abuse with severe polymicrobial infection have been reported [10 - 151, in which most of these infections were intentionally produced by their mother. Forensic pathologists should take into account the physiological and functional changes in abused/neglected children, especially when the cause-
79
of-death was due to infections, e.g. pneumonia, bronchitis, sepsis, etc. But, accurate diagnosis may be difficult since offenders of child abuse seldom tel1 the truth. It is often even difficult to estimate whether physical injuries are intentional or brought on by accident. One important problem in deciding the cause of death is whether the infectieus state was due to child abuselneglect or not. From a medicolegal point of view, victims of child abuselneglect also should not only be protected by the law, but also be regularly examined as to their immune and hormonal states. In conclusion, child abuse/neglect causes thymic involution, which leads to a lowering of immune states. Thymic involution represents an important finding in the estimation of the degree and duration of child abuselneglect. Acknowledgements This study was supported in part by Grant-in-Aid for Encouragement of Young Scientists of the Japanese Ministry of Education, Science and Culture in 1990 (02857095) and in 1991 (03857084). We would like to thank Ms. Kanako Nakagawa (Kobe University) and Mr. Yuuichi Hattori (Hamamatsu University) for their technical assistance. References
8 9 10 11 12 13 14 15
B.D. Schmitt, The child with nonaccidental trauma. In R.E. Helfer and R.S. Kempe (eds.), 2% Buttered Child, 4th ed., The University of Chicago Press, Chicago, 1987, pp. 178- 196. C.H. Kempe, F.N. Silverman, B.F. Steele, W. Droegemueller and H.K. Silver, The batteredchild syndrome. J. Am. Med. Assoc., 17 (1962) 17-24. S.M. Hsu, L. Raine and H. Franger, Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: A comparison between ABC and unlabeled antibody (PAP) procedures. J. Histocha. Qtoch., 29 (1981) 577 - 580. H. Selye, Stress, Acts Inc. Medical Publishers, Montreal, 1950, pp. 452 - 448. A.R. Copeland, A case of panhypogammaglobulinemia masquerading as child abuse. J. Fortmsic Sci., 33 (1988) 1493- 1496. P.L. Morrow, Caffeine toxicity: A case of child abuse by drug ingestion. J. Forensic Sci., 32 (1987) 1801- 1805. S. Kohl, L.K. Pickering and E. Dupree, Child abuse presenting as immunodeficiency disease. J. Pediutr., 93 (1978) 466 - 468. I.M. Roitt, J. Brostoff and D.K. Male, Zmmunology, 2nd ed., Gower Medical Publishing, London, New York, 1989. T. Fukunaga, Discussion of “a case of panhypogammaglobulinemia masquerading as child abuse” with regard to the involution of thymus. J. Forensic Sci., 35 (1990) 232-234. C. Koch and N. Hfiiby, Severe child abuse presenting as polymicrobial bacteremia. Acta Paediatr. Stand., 77 (1988) 940-943. N.A. Halsley, J.M. Frentz, T.W. Tucker, T. Sproles, J. Redding and R.S. Daum, Recurrent nosocomial polymicrobial sepsis secondary child abuse. Lancet, ii (1983) 558 - 560. Y. Zohal, G. Avidan, Y. Shvili and N. Laurian, Otolaryngologic cases of Munchausen’s syndrome. Luryngoscope, 97 (1987) 201-203. T.E. Liston, P.L. Levine and C. Anderson, Polymicrobial bacteremia due to Polle syndrome: The child abuse variant of Munchausen syndrome by proxy. Pediutr., 72 (1983) 211-213. A.J. Palmer and G.J. Yoshimura, Munchausen syndrome by proxy. J. Am. Acad. Child Psychiutry, 23 (1984) 503-508. D. Hodge, 111, W. Schwartz, J. Sargent, J. Bodurtha and S. Starr, The bacteriologically battered baby: another case of Munchausen by proxy. Ann. Emerg. Med., 11 (1982) 205-207.
