Compulrrid Tomographv Pergamon Press 1977. Vol. 1. pp. 103~ 110 Punted in Great Britain

CT EVIDENCE OF GREY MATTER CALCIFICATION SECONDARY TO RADIATION THERAPY

K. FRANCIS LEE and JUNG Ho SUH

Thomas Jefferson University Hospital, Philadelphia, PA 19107. U.S.A.

(Received 24 September 1976)

Abstract-There are four previously reported cases of post-irradiation calcification in the basal ganglia as demonstrated on the conventional skull roentgenograms. We have described two additional cases with grey matter calcification, which were demonstrated 10 and 14yr after radiation therapy for an optic glioma and a medulloblastoma, respectively. The calcification was clearly demonstrated on CT scan, although it was not apparent on the skull roentgenogram. The exact pathogenesis of this condition is not clear. ‘It appears, however, to be related to radiation vasculitis of the small vessels of the brain with resultant hyalinization and calcification. A long-term follow up study would be necessary to evaluate the significance and implication of post-irradiation calcification of the grey matter. CT is the most sensitive method of demon- strating the intracranial calcification in uiuo.

Calcification Roentgenogram Grey matter Radiation vasculitis Post-irradiation

INTRODUCTION

Harwood-Nash and Reilly [S] reported on two children with basal ganglia calcification subsequent to radiation therapy to the head. Since then, Kramer and Lee [9] and Numaguchi et al. [15] have described one case each of post-irradiation calcification in the grey matter. The calcification was demonstrated on the skull roentgenograms taken 10 months to 9 yr after irradiation of the head for various neoplastic conditions of the four reported cases.

During the past two years, we have seen two additional patients with post-irradiation calcification in the grey matter as demonstrated by CT (ACTA scan). Computed tomo- graphy has proven to be extremely helpful in demonstrating both salient and subtle calcification in the brain.

CASE REPORTS

Case 1. A 12 year old girl At the age of 2, she was found to have glioma of the right optic nerve at surgery,

and radiation therapy was given with a tumor dose of 5,500 rad to the suprasellar region through 5 x 5 cm portal using the rotational technique (Fig. 1). She became totally blind in the right eye, but her left vision was normal.

At the age of 9, her vision started deteriorating in the left eye with intermittent headaches, and a pneumoencephalogram showed evidence of an empty sella with no recurrent tumor (Fig. 2). At the age of 12, a CT scan was obtained to determine the cause of the headaches and blurred vision. An extensive calcification was noted in the basal ganglia and posteromedial aspect of the thalamus bilaterally on CT (Fig. 3). In retrospect, there is very subtle calcification in the right basal ganglia in the semiaxial view of the skull (Fig. 4).

Case 2. A 16 year old boy At the age of 2, the patient was found to have medulloblastoma at surgery. A course

of Cobalt 60 treatment was given to the posterior fossa with the tumor dose of 4,700 rad. Approximately 4,300 rad to the supratentorial region and 4,000 rad to the entire spinal

103

104 K. FRANCIS LEE and JUNG Ho SUH

axis were given. The patient did well except for occasional headache and minor seizure disorder. The CT scan in 1975 showed calcification in the basal ganglia and cerebral cortex (Fig. 5).

DISCUSSION

About one half of the patients with parathyroid disorders (e.g. idiopathic, post opera- tive, and pseudo-hypoparathyroidism) demonstrated basal ganglia calcification on skull roentgenograms [14, lo]. Calcification in the grey matter may also occur in carbon monoxide or lead poisoning, Fahr’s syndrome (familial cerebrovascular ferrcFcalcinosis) [l, 2,6,7,12]. Other causes of basal ganglia and paraventricular calcification include tuberous sclerosis, toxoplasmosis, cytomegalic inclusion disease, amaurotic idiocy, and idiopathic cerebral calcification [S, 8,12,15-J.

Microscopic description of bilateral basal ganglia calcification was first made by Virchow [17]. In 1935 Fritzsche [7] was the first to report roentgenologic appearance of basal ganglia calcification in 3 siblings. Its occurrence in idiopathic hypopara- thyroidism was described by Eaton, Camp and Love in 1939 [4]. Basal ganglia calcifica- tion in pseudohypoparathyroidism was first reported by Sprague, Hains, and Power [16] in 1945. Its occurrence subsequent to radiation therapy was first described by Harwood-Nash and Reilly [S] in 1970. Intrathecal administration of Methotrexate may produce intracranial calcification L-141. Kramer and Lee [9] described a case with diffuse calcification in the basal ganglia and cerebral cortex subsequent to irradiation and meth- otrexate (intrathecal) treatment for acute lymphocytic leukemia (Table 1). Nakagaki et al. [13] described monkey brain damage from radiation in the therapeutic range. At six months after 6,000 rad, widely scattered punctate necrotic lesions, 1 mm or less, were demonstrated, whereas, 1 yr later almost complete mineralization of necrotic lesions with innumerable minute deposits of calcium and iron were observed. Vasculitis and telangiectasis were also present.

The pathogenesis of calcification in the grey matter is not clear. Microscopically, vasculitis, fibroblastic process, hyalinization, and calcification were observed in the brains of both humans and animals following irradiation to the heads (Fig. 6). The possibility of an autoimmune reaction localized to the irradiated demyelinated tissue

Table 1. Reported cases of basal ganglia calcification subsequent to radiation therapy

CaSC NO. Author

I. Harwood-Nash 9 and Reilly. 1970

2. Harwood-Nash 3 and Reilly, 1970

3. Kramer and 10 Lee, 1974

4. Numaguchi et al. 9 1974

5 Lee and Sub, 12 1976

6. Lee and Suh, 16 1976

Sex Pathology and site

F Gliohlastoma multlforme in the suprasellar region

M Histiocytosis x involving multiple areas of the

M CNS involvement External cobalt 60 of lymphocytic 550 rad and leukemia methotrexate

F Astrocytoma in the thalamic region

Supervoltage 2 meV resonant transformer, 7 x 7cm” 6.ooO r&d/h weeks

F Spongmblastoma polare, R,ghr optic nerve

M Medulloblastoma cerebellar vermis

Radiation therapy source. field size and

dose

External cobalt 60, 5 x 5cm’ 4,500 tad/4 weeks and 4,500 rad/4 weeks 3 yr later

200 kV X-ray various ports 3COrad x 3. 1,250 rad next year and 1,700 rad following year

External cobalt 60 5 x 5cmz 5.500 rad/5 weeks

Total bran and spine axis 4,ooO tad, 4.700 rad to vermis/ 4: weeks

Duration following radiation therapy

Serum calcium and phosphorus

lW&

3 Y’

9 Yr

IO month

6 yr

IOyr

14yr

Normal

Normal

Normal

Normal

Normal

Normal

JO5

Fig. 1. Case 1 (at age 2). Radiation dosimetry. CoGo with 180” rotational technique and a wedge filter provided 5500 rad in 25 treatments during a period of 5 weeks.

Fig. 2. Case 1 (at age 10). The initial pneumoencephalogram (not shown) demonstrated a suprasellar tumor which was proved to be optic glioma. Seven years later, a second pneumo- encephalogram showed no evidence of tumor mass, the third ventricle being fully expanded (a large arrow). An empty sella (intrasellar herniation of the subarachnoid space) was demon-

strated (small arrows) A “J” shaped sella is still evident. 3v: 3rd ventricle.

106

Fig. 3. gene :OU

Fig.

Jase 1 (at age 12). 10 yr after radiation therapy. A CT (ACTA) shows der calcifications in the grey matter; lenticular nucleus (lateral arrows) and

aspect of the thalamus (lower arrows), bilaterally.

lse hl OIllO- post erior

4. Case 1 (same time as Fig. 3). A semiaxial view of the skull, in retrospect, shows faint linear calcification in the right basal ganglia (arrows).

very

Fig. 5. med Ull’

Fig. 6. by fc ,ca

Case 2. A 16-year-old boy who had Co6’ therapy (4000-4700 rad) at the age ( blastoma. A CT scan shows calcification in the basal ganglia (upper arrow

cerebral cortex (lower arrows).

Post-irradiation calcification in the cerebral cortex. Neuronal cell loss is accorr calcifications in the deeper layers of the cerebral cortex 8 yr after X-irradiation.

(Courtesy of Dr. L. J. Rubinstein).

If 2 for ,‘s) and

lpal nied X 108

CT evidence of grey matter calcification 109

with subsequent accumulation of abnormal metabolites was suggested by Lampert et al. [lo]. Babbitt et al. [ 11 proposed that the ferrqcalcinosis is the end result of a process of circulatory disturbance resulting in local anoxia and necrosis. Harwood-Nash and Reilly [S] postulate that hypersensitivity of small vessels of the basal ganglia to radiation produces vascular damage with hypoxia resulting in calcification. We feel that radiation vasculitis and demyelination due to a localized autoimmune reaction or hypersensitivity to radiation are responsible for hyalinization and eventual calcification in the grey mat- ter. A long term follow up study would be necessary in order to assess the significance and implication of post-irradiation calcification in the grey matter.

Calcifications may not be apparent on the plain skull roentgenograms or even on the tomograms unless sufficient calcium deposit is present. With the use of computerized tomography, we are able to detect both subtle and salient intracranial calcification.

SUMMARY

We have described two cases of grey matter calcification subsequent to radiation therapy. CT is extremely useful in demonstrating subtle calcification in the basal ganglia and cortex. The pathogenesis of grey matter calcification following irradiation has been discussed.

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D. P. Babbitt, T. Tang, J. Dobbs and R. Berk, Idiopathic familial cerebrovascular ferrocalcinosis (Fahr’s disease) and review of differential diagnosis of intracranial calcification in children, Am. J. Roentgenol. 105. 352 (1969). J. C. Bennett, R. H. Maffly and H. L. Steinbach. Significance of bilateral basal ganglia calcification, Radiology 72, 368 (1959). J. D. Camp, Symmetrical calcification of basal ganglia, Radiology 49, 568 (1947). L. M. Eaton, J. D. Camp and J. G. Love, Symmetrical cerebral calcification. particularly of basal ganglia, demonstrable reoentgenographically, Arch. Neural. Psychiat. 41. 921 (1939). C. R. Fitz, C. F. Dereck, D. C. F. Harwood-Nash and J. R. Thompson. Neuroradiology of tuberous sclerosis in children, Radiology 110, 635 (1974). R. L. Friede, K. R. Magee and E. W. Mack, Idiopathic non-arteriosclerotic calcification of cerebral vessels. AMA. Arch. Neural. 5, 219 (1961). R. Fritzsche, Eine familiLr auftretende Form von Oligophrenie mit riientgenologisch nachweisbaren sym- metrischen Kalkablagerungen im Gehirn, besonders in den Stammganglien. Schweiz. Arch. Neural. I/. Psychiat. 35, 1 (1935). D. C. F. Harwood-Nash and B. J. Reilly, Calcification of basal ganglia following radiation therapy, Am. J. Roentgenal. 108. 392 (1970). S. Kramer and K. F. Lee, Complications of radiation therapy central nervous system, Sentin. Roentgenol 9. 15 (1974). P. Lampert, M. I. Tom and W. D. Rider, Disseminated demyelination of the brain following Cob” (Gamma) radiation, AMA Arch. Pathol. 68, 322 (1959). E. V. Medill, Bilateral symmetric calcification of basal ganglia associated with parathyroid insufficiency, Bit. J. Radial. 24, 685 (1951). J. C. Melchoir, C. E. Benda and P. I. Yakovlev. Familial idiopathic cerebral calcifications in childhood. AMA Am. J. Dis. Child. 99, 787 (1960). H. Nakagaki, G. Brunhart, T. L. Kemper and W. F. Caveness. Monkey brain damage from radiation in the therapeutic range, J. Neurosurg. 44. 3 (1976). H. Norrell, C. B. Wilson, D. E. Slagel and D. B. Clark, Leukoencephalopathy following the administration of methotrexate into the cerebrospinal fluid in the treatment of primary brain tumors, Cancer 33. 923 (1974). Y. Numaguchi, J. C. Hoffman and P. J. Sones, Basal ganglia calcification as a late radiation effect, Am. J. Roentgenol. 123, 27 (1975). R. G. Sprague, S. F. Haines and M. H. Power, Metabolic effects of parathyroid hormone, dihydrotachys- terol and calciferol in a case of pseudo-hvpoparathvroidism. J. Lab. C/in. Med. 30. 361 (1945). R Virchow, Kalk-metastasen. Vbchows ,&h: Path.. Anat. 8, 103 (1855).

About the Author-K. FRANCIS LEE was born on I March. 1929, in Seoul. Korea. He received the M.D. degree in 1951 from Severance Union Medical College in Seoul, Korea, and the D.Sc. degree in neuroradiology in 1963 from Yonsei University in Seoul. He was certified by the American Board of Radiology in 1960.

Dr. Lee was Director of the Radiology Research Institute of Seoul from 1963 to 1964 and has been Professor of Radiology at Thomas Jefferson University Hospital since 1971.

110 K. FRANCIS LEE and JUNG Ho SUH

His professional affiliations include American Medical Association, Pennsylvania Medical Society, Philadelphia County Medical Society, Philadelphia Neurological Society, American Society of Neuroradiology, Radiological Society of North America, American College of Radio- logy, American Roentgen Ray Society, College of Physicians of Philadelphia, and the Korean Society of Nuclear Medicine.

About the Author-JuNc Ho SUH was born in Feb. 1939, in Seoul, Korea, and received the M.D. degree in 1964 from the College of Medicine at Yonsei University in Seoul.

Dr. Suh has been Assistant Professor of Radiology at Yonsei University College of Medicine since 1973. He is presently a Fellow of Neuroradiology at Thomas Jefferson University Hospital.