OPTIC CHIASMATIC GLIOMA IN CHILDREN

ALONSO L. DESOUSA, M.D., J O H N E. KALSBECK, M.D., J O H N MEALEY, JR ; , M.D., F O R R E S T D. E L L I S , M.D., AND JANS M U L L E R , M.D.

Indianapolis, Indiana

Although much has been published on optic glioma,1-8 controversy still exists regarding treatment of this lesion. Dien-cephalic syndrome has been reported to be associated with optic glioma, but has not been emphasized as a prominent clin­ical feature. We report herein the results of a study of 26 of 29 patients who had chiasm involvement, 12 of whom had clinical features of diencephalic syn­drome.

MATERIAL AND METHODS

We reviewed records of 29 patients who were seen from 1955 to 1977 with the diagnosis of optic nerve or chiasm glio­ma, or both. Data regarding clinical mani­festations, diagnostic studies, treatment, histologic diagnosis, and follow-up were collected. Association with neurofibro-matosis as well as with diencephalic syn­drome was also noted. The diagnosis was confirmed by surgery in 27 cases.

RESULTS

In 29 patients in whom an optic nerve or chiasm glioma, or both were diag­nosed, optic nerve involvement was found in three. The optic chiasm was involved in 26. Sixteen patients were girls and 13 were boys.

The average age at diagnosis of the optic nerve glioma was 6.2 years in the three cases; in those of optic chiasmatic involvement without diencephalic syn-

From the Departments of Neurological Surgery, (Drs. DeSousa, Kalsbeck, and Mealey), Ophthalmol­ogy (Dr. Ellis), and Neuropathology (Dr. Muller), Indiana University Medical Center, Indianapolis, Indiana.

Reprint requests to Alonso L. DeSousa, M.D., Neurological Surgery Department, Emerson Hall, Room 139, Indiana University Medical Center, 1100 W. Michigan St. Indianapolis, IN 46202.

drome, the average age was 2.3 years, and with diencephalic syndrome 1.1 years (Table 1).

The following clinical manifestations were noted (Table 2): Proptosis was uni­lateral in seven of the patients, optic atro­phy was bilateral in 19. Visual acuity was recorded in 18 patients (Table 3). Five of the patients with rotatory nystagmus had chiasm involvement and also had dience­phalic syndrome. The combination of emaciation, pallor, alertness, and hyper-activity were the most obvious clinical features of the diencephalic syndrome group. None of the patients with dience­phalic syndrome had a family history or clinical signs of neurofibromatosis. Dia­betes insipidus or precocious puberty were not encountered.

Skull x-rays or optic foramen views, or both, were abnormal in 23 of the patients and normal in six. Suture separation indi­cating increased pressure was seen in six patients. The optic foramen views were abnormal in 17 patients, and nine had had bilateral enlargement and eight unilateral enlargement. The air study (pneumoen-cephalogram or ventriculography) and computed tomographic scan indicated su-prasellar mass defined in 23/26 and 5/6 of the cases (Table 4). We were unable to

TABLE 1 A G E AT ONSET AND DIAGNOSIS

Ages Age at Onset Age at Diagnosis (No.) (No.)

<6 mos. 10 4 7-12 mos. 2 5 1-2 yrs 4 6 2-5 yrs 9 7 5-10 yrs 3 6 >10yrs 1 1

376 AMERICAN JOURNAL OF OPHTHALMOLOGY 87:376-381, 1979

VOL. 87, NO. 3 OPTIC CHIASMATIC GLIOMA 377

TABLE 2

CLINICAL MANIFESTATIONS*

Proptosis Optic atrophy Blindness

Unilateral Bilateral

Nystagmus Neurofibromatosis Emaciation (lack of

subcutaneous fat) Pallor Alertness Hyperactivity Hydrocephalus (by PEG){

Optic Nerve in

3 Cases

3 3

3 0 0 1

0 0 0 0 0

Optic Chiasm Without D.S.t

in 14 Cases

5 13

5 1 2

10

0 0 0 2 5

Optic Chiasm WithD.S.+ in 12 Cases

0 10

1 3 6 0

12 5 8 6 7

No.

8 26

13 8

11

11 5 8 8

12

Total

%

27 90

44 27 38

41 17 27 27 41

"Other, less frequent signs included the following: hemiparesis, 4; ataxia, 2; papilledema, 1; athetoid movement, 1.

f D.S. designates diencephalic syndrome. {PEG designates pneumoencephalogram.

differentiate between gliomas occurring primarily in the chiasm and those that secondarily involved the chiasm.

Cerebrospinal fluid was examined in 15 patients, and seven had protein of more than 60 mg/100 ml. In four patients tumor cells were seen in the cerebrospinal fluid; all four had chiasmatic gliomas and dien­cephalic syndrome. The electroencepha­logram (EEG) showed diffuse slowing in seven patients. Focal EEG findings with spike waves, and at times, delta waves were seen in three patients. The EEG was normal in five and not done in 14 patients.

TABLE 3

VISUAL ACUITY IN 18 PATIENTS*

Visual Acuity Right Eye Left Eye Both Eyes

Blindness Decreased acuity Normal vision Not recorded

4 3 4 1

3 3

*Six of the above eyes had visual acuity less than 6/30 (20/100).

Thyroid function studies were normal in five patients tested.

In 27 patients the lesion was surgically confirmed. A resection of the nerve back to the chiasm was done in five patients. In three patients the disease was entirely limited to the nerve, and in two, resection of the nerve was done for relief of disfig­uring unilateral proptosis. Two patients had biopsy with decompression of the canal, 18 patients had radiotherapy, and three patients received BCNU (l,-bis(2-chloroethyl)-l-nitrosourea).

All 12 patients with diencephalic syn­drome were operated on. Two patients in this group died after surgery. Autopsy showed both optic nerves and chiasm involved by tumor as well as the dien-cephalon in one patient. The tumor was classed Group 3 of our histologic pattern. Ten patients had postoperative radiother­apy. All had reversal of their diencephalic syndrome and appropriate increases in weight. Four of these patients died from progression of their disease. They had not had reappearance of the features of the

378 AMERICAN JOURNAL OF OPHTHALMOLOGY MARCH, 1979

TABLE 4 NEURODIAGNOSTIC RESULTS*

No. of Patients

Normal Suprasellar Mass

Accuracy (%)

PEG or VG Brain scan Angiography Computed tomoraphy

26 16 5 6

3 5 2 1

231 11 3 5

68 60 83

*PEG designates pneumoencephalogram; VG, ventriculography. tTwelve of these 23 patients had hydrocephalus.

diencephalic syndrome. Autopsy in one of these patients, who died 42 months after surgery and radiotherapy, revealed a tumor involving the chiasm and dien-cephalon. Six patients are alive and their level of function is shown in Table 5. They were observed up to 11 years. In two cases, no tumor was identified on computed tomographic scanning seven and 11 years postoperatively.

Extension of the tumor from the chiasm, posteriorly, was seen at the time of surgery in 12 patients. Microscopic examination showed a tumor of the astro-cytic series in all cases.

Three distinct histologic patterns could be identified: (1) An acellular pattern, with a solid tissue background, no vas­cular proliferation and almost always Rosenthal fibers. This pattern was preva­lent in patients with neurofibromatosis.

(2) A much more cellular pattern, com­posed of astrocytes, either spindle cells or multipolar, often with a microcystic back­ground and vascular proliferation as well. Patients with optic-chiasmatic involve­ment but without clinical neurofibroma­tosis usually had tumors with this appear­ance. (3) Less cellular, but much more open, honeycombed background, with the microeysts often containing some pro-teinaceous material. Basic tumor cell was always multipolar and vascular prolifer­ation was minimal. This tumor was gelat­inous. This histologic pattern was seen most frequently in patients with clinical evidence of diencephalic syndrome.

There was no evidence of mitosis or infiltration of the contiguous structures in the cases reviewed. Four patients died within one month of operation, three be­fore 1960, and one more recently, also

TABLE 5 L E V E L O F FUNCTION*

Optic Nerve Only

Optic Chiasm Without D.S.

Optic Chiasm With D.S.

Normal function for their age

Retarded Blind and retarded Blind but normal

4 6t 1

*D.S. designates diencephalic syndrome. tHad associated neurofibromatosis.

VOL. 87, NO. 3 OPTIC CHIASMATIC GLIOMA 379

after attempted radical excision of one optic nerve and adjoining chiasm that were massively enlarged from the tumor. No deaths occurred from the optic glioma in the group of patients with neurofibro-matosis. Five patients died subsequently of their tumor five months to 12 years after postoperative radiotherapy; four with diencephalic syndrome. All four probably died secondary to hypothalamic failure caused by tumor growth. The other patient died from a malignant schwannoma of the fifth nerve. Nineteen (65.6%) of the patients in this series sur­vived, 15 of them for more than five years and ten for more than ten years. The 19 survivors included six of the 12 patients with diencephalic syndrome (Table 5).

Of the 11 survivors with optic-chiasmatic involvement without dience­phalic syndrome, four appeared normal clinically. However, one had evidence of persisting tumor by computed tomo-graphic scanning. One patient in this group had a recent computed tomograp-hic scan and no intracranial tumor was seen 20 years after surgery and radiother­apy.

There were two untreated patients with opticochiasmatic gliomas. One patient who had neurofibromatosis, died postop-eratively after an upper cervical laminec-tomy for a glioma of the cord and medul­la. Another retarded and blind child has survived more than ten years without surgery or radiotherapy because of paren­tal refusal.

Two of the three cases with isolated optic nerve glioma are alive. One died of a malignant fifth nerve schwannoma, and 12 years after resection of her optic nerve glioma, no tumor was found in the chiasm at autopsy.

Three other patients had associated tu­mors. All four were patients with neurofi­bromatosis. A cervical cord astrocytoma was found after, an earlier neuroradiologic diagnosis of optic-chiasmatic glioma in

one patient. A plexiform neurofibroma of the seventh nerve and a gasserian gangli­on neurofibroma was found in another patient three years after diagnosis of optic nerve glioma. A plexiform neurofibroma of the orbit was diagnosed on computed tomographic scanning twenty years after resection of the left optic nerve glioma in the fourth patient. Changes in visual acu­ity in fourteen patients are shown in Table 6.

DISCUSSION

Taveras, Mount, and Wood7 found 34 patients with optic chiasmatic gliomas in a series of 2,000 gliomas in all ages. Matson9 reported a 4.5% (27/750) inci­dence of optic chiasmatic tumors among the intracranial tumors seen in his pediat-ric patients. Koos and Miller10 found a 2.3% (16/700) incidence in 700 brain tu­mors among children and adolescents. The management of the optic-chiasmatic glioma is still controversial. There is sup­port favoring surgical or radiation treat­ment, or both,1,6,7 as well as no treat­ment.5,8 Surgical excision has been advo­cated for definitive treatment of isolated optic nerve gliomas. 3-6 '11-13 However, Miller, Iliff, and Green,14 Wong, and

TABLE 6

F O L L O W - U P VISUAL ACUITY IN

14 PATIENTS (1-20 YEARS)

Radiotherapy Visual Acuity and Surgery Surgery Not Treated

Improved 2* 1 -Deteriorated 3 - 1 Unchanged 3 21

*In one of these patients visual acuity was 6/120 (20/400), improved to 6/18 (20/60), but then deterio­rated to no light perception.

fOptic nerve resected, visual acuity remains nor­mal in the other eye.

380 AMERICAN JOURNAL OF OPHTHALMOLOGY MARCH, 1979

Lubow8 recommended no further treat­ment after the diagnosis was made by radiologic and clinical features or biopsy, or both. For chiasmatic glioma with or without gross involvement of the optic nerves the trend is toward radiotherapy as primary treatment with or without tissue diagnosis.1>7,15 Although in some pa­tients there appears to be a correlation of the improvement of visual acuity with radiotherapy,7 patients who were not treated have also had improvement in visual acuity.s '8,16

Hoyt and Baghdassarian5 stated that optic nerve gliomas are a non-neoplastic hamartomatous lesion and no treatment is indicated except for proptosis and relief of the increased intracranial pressure. However, Chutorian and associates1

found evidence of deterioration in two patients in their series, regardless of the maximum possible therapy, and 11 pa­tients died from their disease. Nine of them had increased intracranial pressure. Three of our patients also died regardless of the mode of treatment. Another two patients had recurrence of the tumor 18 months after incomplete resection by a Kronlein approach. Both were reoperated through a craniotomy and a' complete excision was done with no rerecurrence to date. Recently, another patient, ten years after surgery and radiotherapy, had a computed tomographic scan that revealed progressive growth of the optic-chias-matic glioma. These observations are indicative of a progressive neoplastic growth rather than a self-limited or ham­artomatous lesion. Arrest of the progres­sive course has been noted after radio­therapy,1'7 but has also been observed without radiotherapy.5,8 In two of our cases chemotherapy with BCNU (1,-bis (2-chloroethyl)-l-nitrosourea) seems to have been effective.

The gliomas confined to one optic nerve can be cured. If tumor is present in the proximal segment after resection via orbital approach, craniotomy with resec­

tion at the chiasm is indicated. In our experience radical tumor resection in chiasm gliomas did not seem justifiable and the mortality was high after such attempts, although these unsuccessful op­erations were attempted before cortico-steroids and use of the microscope.

All of our cases with the diencephalic syndrome seen from 1955 to 1977 had tumor involving the optic-chiasm. Pelc17

presented three patients with optic chiasm gliomas and diencephalic syn­drome, and in reviewing previously re­ported cases, she noted 70% (17/25) inci­dence of glioma involving the optic nerves or chiasm with this syndrome. This syndrome was reversed by radio­therapy in all of our cases and in 28 other cases reviewed by Burn and associates.18

The effectiveness of irradiation in pre­serving or improving visual acuity could not be established in our series. Although visual acuity improved in one patient after radiotherapy, decreased visual acu­ity to light perception occurred one year later. In another patient visual acuity re­mained improved ten years later. Visual acuity also improved after cortico-steroid therapy and decompression of the optic nerve without irradiation in one patient. Radiotherapy in a young patient may not be a benign procedure, and delayed radia­tion necrosis of the brain may occur.19

The relationship of radiotherapy to men­tal retardation has yet to be established.

We believe all lesions in this location should be confirmed by surgery. A tissue diagnosis should be established to best determine treatment and exclude other lesions, for example, dysgerminoma and craniopharyngioma. Tumors confined to one nerve are potentially curable if total­ly resected; back to the chiasm when necessary. This view is supported by many.2 '3-6,11-13,20 '21 Irradiation may not be necessary postoperatively if a tumor is not seen in the proximal resected nerve.3,6,2°'21

No patient in our series with neurofi-

VOL. 87, NO. 3 OPTIC CHIASMATIC GLIOMA 381

bromatosis died of optic nerve or chiasm glioma. We found no clear evidence sup­porting the effectiveness of radiotherapy in this group of patients. Radiotherapy may, however, reduce proptosis as report­ed by Taveras, Mount, and Wood7 and Chutorian and associates.11

Chiasmatic gliomas without dience-phalic syndrome and without prominent vascular proliferation (histologic pattern 2) may not need postoperative radiothera­py until there is radiologic or clinical evi­dence of progression of the lesion. Dien-cephalic syndrome could be reversed when treated with irradiation. Its effect on longevity and visual acuity in this group of patients is not clear. The value of chemotherapy for optic-chiasmatic glio­mas is not known but the nitrosoureas may be beneficial.

SUMMARY

We reviewed the records of 29 patients with optic nerve or chiasm glioma, or both, seen from 1955 to 1966. Sixteen patients were girls and 13 were boys. At the time of diagnosis, 14 patients were less than 2 years old. Optic atrophy was the most frequently seen physical find­ing, present in 26 of 29 patients. Twelve pa­tients had diencephalic syndrome (41%). Proptosis was seen in eight. Eleven pa­tients (38%) had associated neurofibro-matosis. Pneumoencephalogram was done on 26 patients and was abnormal in 23: The diagnosis was confirmed at sur­gery in 27 patients. All tumors were astro-cytomas. Eighteen patients underwent radiotherapy. Surgery and radiother­apy were used as treatment for optic-chiasmatic glioma with diencephalic syn­drome.

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16. Glaser, J. S., Hoyt, W. F., and Coobett, J.: Visual morbidity with chiasmal glioma. Arch. Oph­thalmol. 85:3, 1971.

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