Symptomatic Arteriovenous Malformation in Infants Less Than 6 Months of Age

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Received for publication Dec 13, 1978; accepted Feb 5, 1979. Reprint requests to (R.P.K.) Department of Pediatrics, Madigan Army Medical Center, Tacoma, WA 98433.

238 PEDIATRICS Vol. 64 No. 2 August 1979

Symptomatic

Arteriovenous

Malformation

in

Infants

Less

Than

6 Months

of Age

Maj

Richard

P. Knudson,

MD, and Lt Col Errol

R. Alden,

MD

From the Department of Pediatrics, Madigan Army Medical Center,

Tacoma, Washington

ABSTRACT. The symptomatology and sequelae of symp-tomatic system arteriovenous (A-V) malformations in

children less than 6 months old make an early diagnosis

possible and early treatment mandatory. A group of 156 infants with systemic A-V malformations involving the CNS (81 infants), liver (61 infants), and lungs (14 infants)

were studied to compare symptoms, diagnosis, treatment, and outcome. Congestive heart failure was present in 67%

of the patients with CNS A-V malformations. Mortality

among the patients with CNS A-V fistulas was 64%. Of

those patients with hepatic A-V malformations 67% had

abdominal masses, 48% congestive heart failure, and 55%

died. Pulmonary A-V malformations presented with con-gestive heart failure 57%, cyanosis 43%, and resulted in a 43% mortality. Early combined medical and surgical

ther-apy offered the best chance for a successful outcome. Pediatrics 64:238-241, 1979; arteriovenous

malforma-tions, congestive heart failure, cavernous hemangioma,

hemangioendothelioma.

Vascular (arteriovenous [A-V]) malformations of the viscera and CNS, although rare in the first three months of life, are responsible for definite

symp-toms including cosmetic problems (facial and limb disfigurement), hematologic derangements, conges-tive heart failure, and CNS abnormalities (in-creased head circumference, hydrocephalus, and

seizures).

Because of the rarity of the lesions, the diagnosis

is seldom entertained and because of the severity of the lesions the outcome is often poor. Therefore, a literature and case review (1940 to 1975) from the

Armed Forces Institute of Pathology was under-taken in an effort to summarize the signs,

symp-toms, diagnosis, treatment, and prognosis of symp-tomatic vascular malformations in infants less than 6 months old.

MATERIAL AND METHODS

A total of 156 cases of vascular malformations were

accumulated through a literature review (124), a

Panlars-Pathology Natural Language Retrieval Search from 1940 to 1975 (30), and personal expe-rience (2). These 156 cases include 81 involving the

CNS, 61 involving the liver, and 14 involving the lungs.

RESULTS

Tables 1 to 4 summarize the pertinent clinical

data concerning CNS A-V malformations in infants

less than 6 months old and can be summarized as follows: The male to female ratio was 2: 1. The most

common symptoms were congestive heart failure (66.6%), bruits (38.2%), murmur (37%), cyanosis

(28.4%), and increasing head circumference (24.7%). The lesions occurred primarily in the vein of Galen (64.2%), the cerebrum involving either the paren-chyma or meninges or both (7.4%), and the superior

sagittal sinus (6.2%). The overall survival was 25.9%, but this increased to 46.8% if only those with antemortem diagnosis were included.

The pertinent data on symptomatic hepatic

vas-cular malformations are illustrated in Tables 1 and 5 and can be summarized as follows: The most common signs and symptoms were an abdominal mass (67.2%), congestive heart failure (47.5%), and cutaneous hemangiomas (30%). The male to female

ratio was 1:1. The pathologic diagnoses were

cay-ernous hemangiomas (34.4%) and

hemangioendo-theliomas (63.9%). The overall survival rate was 44.4%.

The pertinent data on pulmonary vascular ma!-formations are illustrated in Table 1 and can be

summarized as follows: The most common signs

and symptoms are congestive heart failure (57.1%), cyanosis (42.9%), and telangiectasia (28.6%). The

survival rate was 57.1% (67% with sequestration and 50% with primary A-V fistula).

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ARTICLES 239

TABLE 1. Signs and Symptoms of Systemic A-V Fistulas (% of Total)

Sign or Symptom CNS Hepatic

(%) (%)

Pulmonary (%)

Congestive heart failure 66.6 47.5

Bruit 38.2 8.2

57.1

...

Cyanosis 28.4 3.3

Increased head size 24.7 . . .

42.9

...

Seizures 6.2 .. . ...

Cutaneous hemangiomas 4.9 30.0

Prominent facial vascularity 4.9 . ..

Abdominal mass .. . 67.2

28.6

...

Decreased platelets .. . 4.9

Clubbing .. . . ..

Murmur 37.0 . ..

...

21.5

Wheezing .. . . ..

Pneumonia .. . . ..

14.3 7.2

Sex 66.0 50.0 43.0

TABLE 2. Cause of Death in Systemic A-V Fistulas (% of Total Deaths)

Cause of I)eath CNS Liver

(%) (%)

Pulmonary (%)

Congestive heart failure 76 64

Surgical complications 6 16

Hemorrhage 12 8

Sepsis 4 4

Congenital anomalies 2 4

Anemia . . . 4

50 50 ... ... ... ...

TABLE 3. Location of CNS A-V Fistulas

Location No, Total

(%)

Vein of Galen 52 63.2

Cerebral 6 7.4

Superior sagittal sinus 5 6.2

Carotid-jugular 2 2.6

Cerebellum 1 1.25

Frontoparietal 1 1.25

Circle of Willis 1 1.25

Miscellaneous 13 16.0

TABLE 4. Survival for CNS A-V Fistulas

Total no. CNS A-V fistulas 81

Antemortem diagnosis 47

Survivors 21

Survival overall (%) 25.9

Survival limited to those with

ante-mortem diagnosis (%) 46.8

DISCUSSION

The CNS vascular anomalies, represented by

vein of Galen aneurysm, are composed of a tangled mass of tortuous dilated veins, an enlarged artery

feeding the lesions, and an interposed bed of dilated

vessels occupying the position of

arm2

The presenting signs and symptoms may be

thought of as primarily cardiac in the newborn but

neurologic in the infant.

The diagnostic work-up for an intracranial A-V

malformation while not extensive may involve the following: Physical examination will reveal

conges-tive heart failure, bruits, cyanosis, and increased head size. Angiography is the definitive procedure. Cardiac catheterization will demonstrate the rapid recirculation of contrast and the increased oxygen saturation in the superior vena cava. Computed

axial tomography is a noninvasive reliable

diagnos-tic tool.3 Other tests that may be performed are:

skull roentgenographic series which may reveal cal-cification if there is thrombosis of the aneurysm or of the vascular sinus; air contrast, which may

dem-onstrate or suggest a mass in the pineal area;

radio-isotopes, which may demonstrate an increased con-centration in the area of rapid shunting.

The most useful diagnostic procedures are com-puted axial tomography and angiography. The dif-ferential diagnosis of CNS A-V malformations

in-cludes not only metabolic, structural, and infectious

etiologies of seizures, but also the various categories

of congestive heart failure presenting in the

new-born period.4

The definitive treatment of intracranial A-V fis-tulas is surgical. However, medical stabilization of

cardiovascular symptoms with fluid management, diuretics, and digitalis or cardiotonic agents (ie, dopamine, isoproterenol) is required. The best al-ternative to surgical resection, which is ideal but not always feasible, is clipping or ligation of the

afferent vessel of the malformation. After surgery,

persistent heart failure, subdurals, hemiparesis,

sei-zures, and hydrocephalus may complicate recov-ery.5

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sec-TABLE 5. Survival for Hepatic A-V Malformations

240 SYMPTOMATIC ARTERIOVENOUS MALFORMATION

Pathologic Diagnosis No. % Survivors

No. %

Cavernous hemangiomas

Hemangioendotheliomas

A-V fistula umbilicus to liver

21 39 1 34.4 63.9 1.6 10 17 .. . 48.0 43.6 ...

Total 61 . .. 27 44.4

ond major group of symptomatic A-V

malforma-tions, present almost exclusively in the first six

months of life.6 These tumors can be grouped and referred to as hemangiomas that are of two distinct pathologic types. The first group is the cavernous hemangioma, which is a single, large cyst, lined by one layer of endothelial cells, filled with blood, and separated from the normal tissue by connective tissue.6 In contrast, infantile hemangioendothe-liomas are multiple tumor masses lined by several layers of endothelial cells and not separated by connective tissue.6

The triad of clinical findings associated with

he-patic A-V fistulas that should arouse suspicion is hepatomegaly, enlarging cutaneous hemangiomas,

and congestive heart failure.8

The diagnostic work-up for hepatic vascular tu-mors is not extensive and may include the following: arteriography, which is diagnostic and also deline-ates the vascular anatomy for the surgeons; plain films of the chest, which wifi delineate the heart size and vascularity; posterior-anterior and lateral abdominal films, which may show a mass displacing

the colon downward; ultrasonography;9 routine lab-oratory tests, which are nonspecific but may show a normocytic normochromic anemia, an increased

biirubin, a microangiopathic hemolytic anemia, and an increased SGOT.

Therapy includes the following: partial

hepatec-tomy-a form of therapy only possible in single lesions, usually cavernous hemangiomas, and only

rarely in an infantile hemangioendothelioma local-ized to a single lobe of the liver;’#{176}hepatic artery ligation-obliteration of the artery feeding the vas-cular tumor, used in diffuse lesions; in this series,

surgery for hemangioendothelioma resulted in 73% survival but medical management (digitalis, ste-roids, and irradiation) resulted in only 22% survival; steroids-mechanism of action is unknown but the platelet count may increase and the tumor and

symptoms may regress.”

Pulmonary A-V fistulas fall into two major clas-sifications: isolated A-V fistulas (sequestrations) and primary A-V fistulas (multiple or telangiectatic

fistulae). The signs and symptoms associated with

pulmonary arteriovenous fistulas vary with the age of onset. Approximately one half of the pulmonary A-V fistulas present in the newborn period with

cyanosis or clubbing or both.’2 Other early

symp-toms include dyspnea, decreased oxygen saturation, and polycythemia. A murmur that may be heard over the posterior chest and axilla on the affected

side is characterized as a 1-3/6 harsh blowing, pan-systolic murmur. A murmur with a lower lobe

den-sity on chest x-ray should alert the physician to the

possibility of a sequestration.

The diagnosis is suspected from the clinical signs of cyanosis, polycythemia, murmur, and cutaneous

telangiecta.sia. Confirmation is made by chest x-ray, tomography, and contrast echocardiography. An

arteriogram or cardiac catheterization will provide

the definite diagnosis except for telangiectatic

pul-monary A-V fistulas.

The treatment is primary surgical but this is only practical in single or multiple lesions confined to an

isolated area of the lung.

SUMMARY

Vascular malformations that produce symptoms

in the first six months of life are seen primarily in

the CNS, lung, and liver.

These lesions, despite their cluster of symptoms, are not often considered in the differential

diagno-sis. The work-up is not extensive but it is invasive in that cardiac catheterization or angiography or both are required for definitive diagnosis. Once the diagnosis is made, the management of choice is a combined medical-surgical approach.

ACKNOWLEDGMENT

The authors thank Drs Kamal G. Ishak and Thomas

Stoecker of the Armed Forces Institute of Pathology for their review of the pathologic data and Mrs Klara Keen

for typing the manuscript.

See NAPS document No. 03429 for 12 pages of

supple-mentary material. Order from NAPS do Microfiche

Pub-lications, P. 0. Box 3513, Grand Central Station, New York, NY 10017. Remit in advance, in US funds only

$5.00 for photocopies or $3.00 for microfiche. Outside the

US and Canada add postage of $3.00 for photocopy and $1.00 for microfiche.

REFERENCES

1. Ford FR: Diseases of the Nervous System in Infants and Childhood. Springfield, IL, Charles C Thomas,

1970, p 1034

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ARTICLES 241

2. Cronquist 5, et a!: Hydrocephalus and congestive

heart failure caused by intracranial arteriovenous

malformation in Infants. J Neurosurgery 36:249, 1971

3. Harwood-Nash DC, et al: Computed tomography in children. J Pediatr 89:343, 1976

4. Silverman BK, et at: Congestive heart failure in the

newborn caused by cerebral A-V fistula. Am J Dir Child 89:539, 1959

5. Amacher AL, et al: Syndromes and surgical treatment of aneurysms of the great vein of Galen. J Neurosurg 39:89, 1973

6. Dehner LP, Ishak KG: Vascular tumors of liver in

infants and children. Arch Pathol 92:101, 1971 7. Moss AA, et al: Angiographic appearance of benign

and malignant hepatic tumors in infants and children.

Radiology 113:61, 1971

8. Touloukian RI: Hepatic hemangioendothelioma.

Pe-diatrics 45:71, 1970

9. Wilson DA: Ultrasound: Applications in the pediatric

heart and abdomen. Curr Probl Pediatr 1978 10. Matolo NM, et a!: Surgical treatment of hepatic

hemangioma in newborns. Arch Surg 106:725, 1973

11. Rocchini AP, et al: Hepatic hemangioendothelioma: hemodynamic observations and treatment. Pediat-rics 57:131, 1975

12. Higgins CB, et al: Clinical and angiographic features of pulmonary A-V fistulas in children. Radiology 119:

117, 1976

PRINCESS ELIZABETH, SECOND DAUGHTER OF

RICKETS

KING CHARLES I, AND

In 1856 the coffin of Princess Elizabeth (1635-1650) was discovered during

the demolition of old St. Thomas’s Church at Newport, Isle of Wight, England.

Mr. Ernest P. Wilkins, MRCS, examined the remains of the Princess and

noted:’

The bones of the upper arm were slightly curved outwards-more particularly the right humerous-while those of the forearm were somewhat twisted and considerably curved outwards. The spinal column, retaining the relative position of the vertebrae during life, presented an extremely curved condition constituting the double lateral or S

curvature of pathologists, which must have caused considerable projection of the right

shoulder-blade and its attendant deformity . ...

The condyles of the lower extremities were very large in relative proportion. The femur or thigh bone of the left side was curved forwards and inwards, that of the right side was more distorted than any other long bone. It was very much curved forwards and inwards. This bone was much flattened, its greatest diameter being from before, obliquely

outwards and backwards; the concavity of the curve was somewhat filled in, and the

bone thus strengthened by additional osseous deposit in accordance with the natural reparative tendency of Nature’s laws. The bones of the leg, the tibia and fibula, were much curved outwards.

The bones of the skeleton indicate the great deformity which existed during life-there

was evidently considerable “growing out” of the right shoulder-blade and corresponding

flattening of the left side of the back. The lower extremities were contorted and of unequal length, the knees were what is termed “knocked”; below the knees the legs were bowed, the heels thrown outwards and the toes inverted. This, with the description of

the skull alone, will sufficiently convey an idea of her personal appearance when living.

It is clear she suffered from rickets in an advanced degree.

It is of interest that Princess Elizabeth died in 1650, the same year that

Francis Glisson’s De Rachitide was published. This treatise on rickets is re-garded as the most important work which had yet appeared on the subject.2

Noted by T.E.C., Jr, MD

REFERENCES

1. Burland C: An historical case of rickets. Practitioner 100:391, 1918

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1979;64;238

Pediatrics

Richard P. Knudson and Errol R. Alden