- Email: [email protected]
Acquired Nystagmus in Early Childhood
Acquired Nystagmus in Early Childhood: A Presenting Sign of Intracranial Tumor MARY A. LAVERY, MD,* JOHN F. O'NEILL, MD,t FRED C. eHU, MD,; LOIS J. MARTYN, MD§
Abstract: This study is a multicenter, retrospective report of 10 infants in whom acquired nystagmus was the initial sign of chiasmalfparachiasmal glioma. Nine patients presented before the age of 10 months. The nystagmus, primarily described as pendular and asymmetric, was difficult to differentiate from and therefore most often diagnosed as spasmus nutans. On average in the ten patients, the intracranial glioma was not recognized for 8.6 months after the onset of nystagmus. In the five diagnosed as spasmus nutans, the mean delay in recognizing the tumor was 14.5 months. Three associated clinical findings were present or developed in these patients to distinguish this entity from spasmus nutans: optic atrophy in all ten patients, poor feeding due to diencephalic syndrome in 5 of 10, and increased intracranial pressure with hydrocephalus in 3 of 10. The acquired nystagmus in these infants was evidence of a life-threatening chiasmalfparachiasmal glioma. [Key words: acquired nystagmus, anterior visual pathway glioma, chiasmatic-optic nerve-hypothalamic astrocytoma, congenital nystagmus, diencephalic syndrome, spasmus nutans.] Ophthalmology 91 :425-435, 1984
Nystagmus in early childhood can present a diagnostic dilemma for the examining ophthalmologist. Because the majority of such cases are benign and unrelated to neurologic disease, attention has most often been drawn to distinguishing congenital nystagmus from spasmus nutans.
From The Wilmer Eye Institute. Johns Hopkins University Hospital, Baltimore, Maryland: the Department of Ophthalmology. Childrens Hospital National Medical Center. Washington, DC and Center for Sight, Georgetown University Medical Center. Washington, DC,t the National Eye Institutes, National Institutes of Health. Bethesda, Maryland,~ and the Department of Ophthalmology and Pediatrics, Temple University School of Medicine and SI. Christopher's Hospital for Children, Philadelphia.§ Presented at the Eighty-eighth Annual Meeting of the American Academy of Ophthalmology. Chicago, Illinois, October 30-November 3, 1983. Supported in part by a Heed-Richard G. Scobee Memorial Fellowship Grant and a National Children's Eye Care Foundation Research Award. Reprint requests to John F. O'Neill, MD, Department of Ophthalmology, Center for Sight, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, DC 20007.
Occasionally, acquired nystagmus in infancy has been the first sign of life-threatening chiasmal or parachiasmal gliomas. 1-8 The occurrence of these cases is rare, so careful evaluation of such children for associated ophthalmologic, neurologic, or systemic signs is important. This report analyzes the medical histories of ten patients from seven medical centers.
MATERIALS AND METHODS After reporting two cases of acquired infantile nystagmus with diencephalic syndrome due to intracranial glioma,9 we solicited similar cases from a number of major ophthalmic centers. Information was collected on a total of ten patients who met the criterion; acquired infantile nystagmus was the initial sign of intracranial glioma. Six of the ten were examined by one or more of the authors. Five other cases offered were not considered in the study because the nystagmus appeared as a late sign in the course of disease. 425
OPHTHALMOLOGY •
MAY 1984 •
VOLUME 91
•
NUMBER 5
Fig 1. Left. noncontrast cranial CT of case I at age 10 months demonstrating large, suprasellar hypolucent areas. Right. contrast enhancement revealing large, lobulated partially cystic hypothalamic astrocytoma.
Three case histories of acquired nystagmus were selected to highlight aspects of the disease process which led to further diagnostic workup: inanition, hydrocephalus, and optic atrophy.
CASE REPORTS Case 1. Acquired Nystagmus with Subsequent Inanition. At age 6 months a healthy girl was noted by the parents to have slow horizontal oscillations of her left eye; a similar pattern of movement began in the right eye I week later. The infant was the product of a full-term uncomplicated gestation and normal delivery with a birth weight of 8 Ibs, II oz. All growth and developmental milestones were appropriate and normal. During ophthalmological examination, asymmetrical nystagmus was noted and described as "slow, horizontal, pendular, and irregular." There was infrequent and irregular head nodding, but no deviation of the eyes or torticollis was observed. Good fixation and following movements and normal pupillary responses were present in each eye. The optic nerve heads showed no evidence of atrophy or papilledema. The provisional diagnosis was acquired nystagmus, probably spasmus nutans. Two weeks later the asymmetric slow horizontal nystagmus was still present with the addition of occasional small amplitUde vertical and torsional eye movements. Sporadic head nodding was still noted without torticollis. At the age of 8 months the
426
infant was seen at the National Eye Institute. Although the child's eyes were steady at times, horizontal conjugate pendular nystagmus was present, characterized by a frequency of I to 2 Hz and an amplitude of less than 50. Interspersed were bursts of smaller, vertical pendular oscillations which were intermittently conjugate and disconjugate. When disconjugate, the vertical movements were either similar to "seesaw" nystagmus, or one eye moved vertically while the other moved horizontally. Occasionally, oblique or circular oscillations were noted. Head nodding was infrequent and did not appear to be correlated with the eye movements. The pattern of nystagmus was unlike that in spasmus nutans because of its relatively low frequency of oscillations, and unlike that in congenital nystagmus because of its irregular pendular pattern. During this examination, the additional history of irritability, ambivalence to feeding and weight stabilization was obtained. It was recommended that the child undergo further neurological studies and CT scanning. Several weeks elapsed while the family was reluctant to have the child studied radiologically. At 9 112 months a neurologist found her to be normal except for slight hypotonia with hyperreflexia of the lower extremities. The infant began to lose weight and at age 10 months cranial CT scan demonstrated a large, intrinsic, partially cystic intracranial mass in the hypothalamic area (Fig I). Angiography demonstrated displacement of the cerebral arterial system bilaterally, and confirmed the presence of a suprasellar mass. Right frontal craniotomy revealed an encapsulated chiasmatic/hypothalamic lesion infiltrating the right optic nerve and displacing the left. Histopathologic di-
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Fig 2. Left, bilateral optic atrophy in case I at age 22 months, greater in the right eye than in the left eye (right).
agnosis was low-grade astrocytoma. A total of 4500 rad was administered over a 4-week period beginning 2 weeks postoperatively. At 22 months follow-up the child enjoyed good general health with increased appetite, good food intake, and progressive weight gain. Although the nystagmus was diminished, bilateral optic atrophy developed which was greater in the right eye. (Fig 2) There was an increasing esotropia with poor abduction of both eyes. (Fig 3) She underwent recession of both medial rectus muscles at age 2 years.
nystagmus. There was decreased vision of the right eye and right exotropia along with bilateral optic nerve pallor, greater on the right. At age 32 months, four small cafe-au-Iait spots were noted but were not considered sufficient to justify a diagnosis of neurofibromatosis. The most recent ophthalmologic exam at age 45 months noted a decrease in the nystagmus. The right eye has eccentric fixation, exotropia, and marked optic atrophy, and left eye central, unsteady maintained fixation and moderate
COMMENT
Pendular asymmetric nystagmus was the presenting sign of an intracranial glioma. When signs of the diencephalic syndrome became apparent, CT scan disclosed a tumor involving both the optic chiasm and hypothalamus. Although the tumor resolved following radiation therapy, bilateral optic atrophy developed. Case 5. Acquired Nystagmus with Subsequent Papilledema. A 3-month, l-week-old girl was noted by the parents to have the onset of nystagmus in her left eye only. The infant was the product of an uncomplicated full-term gestation and delivery. Development had progressed normally. Examination the following week by a pediatric ophthalmologist disclosed a bilateral small-amplitude high-frequency horizontal nystagmus which was greater in the right eye. Good fixation was obtained in the right eye but only central unsteady fixation in the left. The pupillary responses and posterior poles were normal. The diagnosis was spasmus nutans. On reexamination I week later, the patient was noted to have papilledema. CT scan demonstrated a large spherical 5-cm contrast-enhancing mass extending from the sella to the level of the foramen of Monroe. At craniotomy, the tumor was found to arise from the chiasm and extend into the left optic nerve and the hypothalamus. The tumor was biopsied, the left orbit decompressed, and bilateral subdural-peritoneal shunts inserted. Histopathologic diagnosis was astrocytoma, Grade II. A course of radiation therapy totalling 4500 rad was delivered to the tumor field. At age 10 months the patient developed left-sided weakness secondary to a right cerebrovascular accident. At age 24 months a single seizure occurred and on ophthalmologic exam there was persistence of pendular, small amplitude, rapid, horizontal
Fig 3. Progressive esotropia in case I at 22 months of age here at II months after craniotomy and 10 months after completion of radiation therapy.
427
OPHTHALMOLOGY
•
MAY 1984
•
VOLUME 91
•
NUMBER 5
Table 1. Characteristics of Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathway
Case No.
2 3 4 5 6 7
8
9
10
Age of Onset of Nystagmus (months)
Sex
Unilateral or Bilateral
6
F
5 5% 5 3114 23 7213
M M M F M M F F M
9
4
93/.1
Frequency
Amplitude
Rhythm
Pattern
Asymmetry
U----B
Slow
Small
Pendular
Hvoc
+
Variable
U B U-B U-B U-B U U U-B U-B
Slow Rapid
Moderate
U
Rapid
Small
H Hvot Hvct H
+ + +
U Conjugate Conjugate
Slow
Large Small
U U
U U
Rapid
Small
Mixed Pendular Pendular Pendular Pendular Pendular Pendular
V H Vr H
+ +
Conjugacy
Initial Diagnosis Acq. nyst., possibly spasmus nutans Diencephalic syndrome Acq. nyst. Spasmus nutans Spasmus nutans Acq. nyst. and O.A. Acq. nyst. and OA Acq. nyst. and O.A. Spasmus nutans Spasmus nutans
M = male; F = female; U = unilateral only; B = bilateral only; U ---+ B = started unilateral and became bilateral; H = primarily horizontal; v, 0, c, r, t = lesser components of vertical, oblique, circular, rotary, or torsional nystagmus; V = primarily vertical; Acq. nyst. = acquired nystagmus; OA = optic atrophy.; - = not stated.
optic atrophy. CT scan at age 49 months revealed no evidence of residual tumor. The patient has delayed mental development. COMMENT
This case demonstrates rapid asymmetric pendular nystagmus highly suggestive of spasmus nutans as the presenting sign of intracranial glioma. Although the fundi were initially normal, papilledema was noted the following week. At the time of tumor, biopsy shunting procedures were necessary and shortly thereafter radiation treatment was given. The subsequent course included bilateral optic atrophy with decreased vision. Case 8. Acquired Nystagmus and Optic Atrophy. This 9-month-old girl presented with a 2-week history of unilateral nystagmus and intermittent exodeviation of the right eye. The patient was well-developed, well-nourished and had a normal gestation, delivery and perinatal period. There was no family history of nystagmus or neurofibromatosis. Examination revealed good fixation of the left eye, but no fixation of the right could be elicited. Both pupils reacted well to light. There was a fine unilateral horizontal pendular nystagmus of the right eye. Neither head nodding nor torticollis were present but there was an intermittent variable right exotropia. The maculae were normal. The left optic nerve head was normal. However, equivocal pallor and flattening of the right optic disc prompted further neurological workup. CT scan demonstrated an intensely enhancing solid tumor measuring up to 24 mm in diameter, situated above the planum sphenoidale and filling the sella turcica. There was no evidence of hydrocephalus. Cerebral angiography confirmed the presence of an avascular, suprasellar mass. Curiously, the monocular nystagmus in the right eye ceased on the day prior to surgical intervention. Surgery revealed that the large tumor involved the optic chiasm, the right optic nerve and tract, and left optic nerve. Subtotal resection was performed. The histopathologic diagnosis was astrocytoma Grade I or II. A right afferent pupillary defect was detected immediately postoperatively. Vincristine and Actinomycin D were administered.
428
In the follow-up examination 1 month later, nystagmus was not present. Visual response in the right eye to large objects was obtained just in the infero-temporal field. The left eye had good fixation. Pupillary reaction to light in the right eye was decreased and the left eye was normal. The right optic disc was slightly pale, the left optic disc was normal. There was a 25prism diopter right exotropia. CT scan at age 13 months showed a decrease in the extent of the tumor with the presence of cysts within the tumor. COMMENT
Acquired uniocular nystagmus and minimal optic atrophy were the presenting signs of intracranial tumor. No other localizing neurologic signs or symptoms were' present. Interestingly, the nystagmus in the right eye was transitory and ceased prior to surgical or chemotherapeutic intervention.
RESULTS With the exception of one patient, the onset of nystagmus occurred before the age of 10 months (Table 1). In nine of ten patients, the nystagmus was initially unilateral; one patient had bilateral nystagmus from the onset. Of the unilateral cases, six eventually manifested bilateral nystagmus. Throughout the course of observation, the nystagmus remained unilateral in the other three patients. In the majority of the cases, the nystagmus was pendular and asymmetric. It was purely pendular in seven patients, and mixed pendular/jerk in one patient. No patient had isolated jerk nystagmus. In the bilateral cases where the comparison was made, asymmetry was noted. Three other cases were unilateral, which by definition would be asymmetric. Several other characteristics ofthe nystagmus were less consistent. Horizontal nystagmus was prominent, but
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Table 2. Ophthalmic Findings at Presentation in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No.
Head Nodding
1 2 3 4 5 6 7 8 9 10
+
Torticollis +
+ +
+ +
+
Vision OD/OS +F/+F +F/+F +F/+F +F/+F C?SM/U !V/lV no F/+F no F/+F +F/+F +F/+F
Optic Atrophy OD/OS
-/-
-/?/?
-/-
+/+ +/+/-
-/-/-
Pupillary Reactions nl nl nl nl nl nl !OD/nIOS nl nl nl
Afferent Pupillary Defect
None
+00
Strabismus
Neurofibromatosis
Family History of Nystagmus
X(T)OD
X(T)OD +
+ = present; - = not present; - = not stated; 00 = right eye; OS = left eye; F = Fixation; C?SM = central, questionable steadiness, maintained fixation; U = unsteady fixation; !V = decreased vision; ?/? = questionably pale disks OU; nl = normal; X(T) = intermittent exotropia.
variable degrees of vertical, oblique, circular, or torsional nystagmus were also described in three patients. Two other patients had primarily vertical nystagmus, involving one eye in one patient, and both eyes in the other. Where recorded, the nystagmus was most often of small amplitude (four of six patients), but one patient had moderateamplitude and another had wide-amplitude nystagmus. The frequency was rapid in three cases and slow in three others. Head nodding, torticollis, or both were present in six of ten cases (Table 2). Spasmus nutans was diagnosed in five cases and these were followed for 1 week to 41f2 years before a second sign prompted further neurologic studies. Initially, normal fixation was present in six of ten patients. Four others had decreased vision, either unilaterally or bilaterally. In only one case was an afferent pupillary defect seen. Initially, nine of ten cases had normal pupillary responses. Strabismus was present in two cases and subsequently developed in five others. Optic atrophy was initially present in only three cases, unilateral in two patients, and bilateral in one. When optic atrophy was
observed, this finding resulted in further investigation for intracranial tumor. The interval between onset of nystagmus and diagnosis of glioma ranged from 15 days to 54 months (average, 8.6 months). In the five patients discussed as spasmus nutans, the average delay in recognition of the glioma was 14.5 months. The delay in one case of 6 months could be attributed in part to a strong family history of nystagmus (maternal grandmother, maternal great uncle) and a history of head nodding in the fraternal twin. None of the patients had neurofibromatosis. One case had four small cafe-au-Iait spots, but these were deemed insufficient evidence to establish a diagnosis of neurofibromatosis. In eight cases, no evidence for neurofibromatosis in the family history could be found. Two associated systemic conditions commonly occurred which necessitated further workup: diencephalic syndrome and hydrocephalus (Table 3). Diencephalic syndrome was recognized in one-half of the cases, the earliest concurrently with presentation, the latest 9 months after the onset of nystagmus. One patient developed pap-
Table 3. Systemic Findings in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Age of Onset of Nystagmus (months)
Case No.
6 5 5V2 5 3% 23
1 2 3 4 5 6 7 8 9 10 +
7213 9% 4 93/.1
=
present; -
=
Second Sign or Symptom
Age at second Sign/Symptoms (months)
Poor feeding Poor feeding Optic atrophy & hydrocephalus Poor feeding Papilledema & hydrocephalus Optic atrophy Poor feeding Optic atrophy Optic atrophy Poor feeding
8 10 25 6% 3% 28 7213 10 58 15
not present.
Diencephalic Syndrome + + +
Hydrocephalus
+ +
+
+
+
+
Age at Tumor Diagnosis (months)
Interval from Onset of Nystagmus to Tumor Diagnosis (months)
10 10 6 10 4% 29 8213 10% 58· 18
4 5 % 5 1% 6 1 1% 54 8%
• Presumed optic glioma.
429
OPHTHALMOLOGY
•
MAY 1984 •
VOLUME 91
•
NUMBER 5
Table 4. Extent of Tumor Involvement in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No.
Diagnosis
Biopsy proven
1 2 3
Astrocytoma, low grade Astrocytoma, grade II Astrocytoma, grade II
yes yes yes
4 5
Optic glioma, grade I Astrocytoma, grade II Optic glioma Astrocytoma, grade I Astrocytoma, grade I-II Presumed optic glioma Astrocytoma, grade II
yes yes yes yes yes no yes
6
7 8
9
10
Tumor Involvement RON
LON
Chiasm
Hypothalmus
+
+"
+
+
+ + +
+ + +
+
+ + +
+ + + + + + +
+ +
+ + + + +
+ + +
Other
Right frontal and temporal lobes, thalamus; later ascites ftuid.
+
Right optic tract Right & Left optic tracts, midbrain, diffuse subarachnoid nodules, cerebellum, spinal cord; ablation of the pituitary gland 20 to radiation (autopsy).
+
RON = right optic nerve; LON = left optic nerve; + = present. " Optic nerve displaced laterally.
illedema as evidence for hydrocephalus 2 weeks after onset of the nystagmus. Three other patients developed hydrocephalus during their course of follow-up after tumor diagnosis. A diagnosis of intracranial glioma was established in all ten of these patients (Table 4). In nine it was histopathologically proven, with eight classified as low grade. All ten had demonstrable optic chiasmatic involvement. Where the hypothalamus was affected, diencephalic syndrome or hydrocephalus was invariably present. Follow-up after tumor diagnosis of the glioma (Table 5) averaged 48.5 months (range, 4-69 months). Radiation therapy to the site of the tumor was administered in nine of ten patients. Three patients received chemotherapy. The nystagmus disappeared in three patients, decreased
in three and was unchanged in two others. In another patient, it converted to unilateral roving nystagmus. In one patient examined at age 58 months, CT scan revealed "seesaw" nystagmus and optic atrophy with enlargement of the optic chiasm and both optic nerves. On follow-up CT (Table 6), one case showed complete resolution of tumor while four showed a decreased tumor size (Fig 4). No change was seen in two cases while tumor enlargement occurred in three cases. Nevertheless, all 10 cases developed progressive optic atrophy. On follow-up, an afferent pupillary defect was recorded in eight of ten cases. Four of five patients with diencephalic syndrome improved after radiation therapy; one patient had recurrent inanition when tumor growth recurred. Two patients fol-
Table 5. Ophthalmologic Outcome in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No. 1 2 3 4 5
6 7
8
9
10
Therapy Radiation 4500 r Radiation 4500 r Radiation 5040 r & chemotherapy Radiation 4000 r Radiation 4500 r Radiation 5550 r Radiation 4500 r & chemotherapy Chemotherapy Radiation 4500 r Radiation 5000 r
Follow-up (months)
Nystagmus
Vision
Afferent Pupillary Defect
Optic Atrophy
Strabismus
+OD +OD
OD> OD OD> OS OD> OS
ET OS XT OD X(T)OD
66
42
Decreased Ceased Decreased
Poor F; +F 5/400, 20/25 3/200; 8/200
154 42
Continued Decreased
NLP; NLP Eccentric; central unsteady 20/30; HM NLP; 20/30
OU amaurotic
OU OD> OS
XT OD
+OS OD amaurotic
OD> OD OD> OS
X(T)OD
Peripheral field; +F Unsteady; 20/80 NPL; 20/400
+OD +OD OD amaurotic
OD only OD> OS OD> OS
22
51 27 4 8
69"
Ceased Continued OD roving Ceased Seesaw OD > OS Continued
XT OD None
r = rad; F = fixation; NLP = no light perception; HM = hand motion; ET = esotropia; XT = exotropia; X(T) = intermittent exotropia; OD = right eye; OS = left eye; OU = both eyes; - = not stated. " Died at 7 yrs, 3 mos.
430
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Table 6. Medical Outcome in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No. 1 2 3
Follow-up (months)
Therapy
Shrinkage Dramatic shrinkage Enlargement at age 25 mo. No change Complete resolution
Resolived Resolved None
+
Resolved None
+
4 5
6
Radiation 5550 r
51
Shrinkage
None
7
Radiation 4500 r & Chemotherapy
27
Resolved
8
Chemotherapy Radiation 4500 r Radiation 5000 r
Initial shrinkage; age 70 mo; enlargement Shrinkage No change Enlargement, then extension & diffuse CNS seeding
10
r = rad; n = normal; GH " Died age 7 yrs, 3 mos.
66
42
154 42
4
8
69"
=
CSF Shunt Procedure(s)
Inanition
Radiation 4500 r Radiation 4500 r Radiation 5040 r & Chemotherapy Radiation 4000 r Radiation 4500 r
9
22
CT Tumor Response
growth hromone; R = right; CVA
=
lowed for more than 5 years developed growth hormone deficiency. One of these also had adrenal insufficiency and diabetes insipidus 1 year before dying from progressive hydrocephalus, mental deterioration, and shunt infection.
DISCUSSION We have reviewed records of ten patients, from seven centers, with acquired nystagmus as the first sign of an intracranial glioma. Nine of ten patients were less than 10 months of age when the nystagmus was first observed; the remaining patient was 23 months of age. The nystagmus was typically pendular and asymmetric. In nine of ten patients the nystagmus was unilateral initially; in six it became bilateral, while in three it remained unilateral. The nystagmus was horizontal in seven of nine cases. But there were episodes of vertical, oblique, torsional, or circular nystagmus in three patients and two patients had primarily vertical nystagmus. Six patients had associated headnodding, torticollis, or both. The acquired nystagmus seen in this condition must be distinguished principally from spasmus nutans, a benign condition with asymmetric nystagmus, head nodding and torticollis,IO and from congenital nystagmus. It was impressive that five of the ten patients in our series were initially diagnosed as having spasmus nutans, leading to a delay in recognition of the intracranial tumor for an average 14.5 months. The nystagmus and head nodding in patients with the gliomas were similar to that in spasmus nutans. The onset of nystagmus in both conditions most often occurs prior
Neurologic Status
n GH deficit
Mental retardation
n n
+
None None Improved, then recurred
cerebrovascular;
Endocrine Status
+
Small stature n n GH deficit, Adrenal insufficiency Diabetes insipidus
+
=
present; -
=
not present; -
=
Mental retardation R CVA, seizures, Mental retardation R hemiparesis n intellect n n n Progressive hydrocephalus, infection, death
not siated.
to age one year. IO The description of rapid, fine asymmetric nystagmus in two of our cases with gliomas was similar to that of spasmus nutans. The finding of both head nodding and torticollis in one of these patients made the distinction from spasmus nutans especially difficult. Finally, as in spasmus nutans, the nystagmus in six of our ten cases decreased or resolved in follow-up. Interestingly, none of the cases we reviewed were labelled congenital nystagmus, which would be typically recognized as being horizontal, conjugate and relatively regular, whether jerk or pendular. II One of our cases was diagnosed as spasmus nutans despite a strong family history of nystagmus. Tables 7 through 9 summarize ten previous case reports where acquired infantile nystagmus was the initial sign of an intracranial tumor. I-8 There were striking parallels between the summaries of those reports and our observations. Spasmus nutans was the initial diagnosis in half of those reports. The onset of nystagmus ranged from 1 to 36 months; seven of ten were age 12 months or less. Where stated, the nystagmus was described as pendular and asymmetric. Five of those 10 cases had rapid frequency nystagmus. Head nodding, torticollis or both were described in half of the previous reports. Other similarities included the diagnosis of low-grade chiasmal glioma, relatively infrequent optic atrophy on the initial visit (three of eight cases), and tumor involvement of one or both optic nerves (eight of ten cases). In other studies of anterior visual pathway gliomas l2 - 17 the frequency of nystagmus in patients with chiasmatic gliomas ranged from 9 to 42%. Chutorian et al 12 specifically mentioned nystagmus as an initial sign in 8 of their
431
OPHTHALMOLOGY •
MAY 1984 •
VOLUME 91
•
NUMBER 5
Fig 4. Top left, contrast-enhanced cr scan of case 2 at age II months, showing a large cystic hypothalamic astrocytoma prior to radiation therapy. Top right, marked reduction in tumor size after completion of radiation ' therapy (4500R). Bottom left, complete resolution of hypothalamic tumor shown on contrast-enhanced cr 3 years after radiation therapy.
13 patients with chiasmal gliomas. It was also clear that the occurrence of nystagmus in chiasmatic gliomas was age-dependent; it was seen mainly in younger children. The best delineation of such a relationship was the study
432
of Miller et alY In the patients aged 6 years or less, 8 of 21 developed nystagmus, 4 ofthese 8 were younger than 1 year of age. In contrast, no patients 10 years of age or older had nystagmus. The anatomic location of the glioma
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Table 7. literature Review of Acquired Nystagmus as a Presenting Sign of Intracranial Glioma of the Anterior Visual Pathway
Author
Age of onset of Nystagmus
Sex
Udvarhelyi 1 Donin 2 Donin2 Ciccarelli 3 Kellt Add y5 Schulman 6 Ant ony 7 Ant ony 7 Koenig 8
3y 31 m 7m 1m 8m 5m 3y 13 m 10 m 4m
M M M M M F M F M F
Unilateral or Bilateral
Amplitude
Frequency
U U U B B U-B U-B U-B U
8
Rapid Rapid Slow Rapid Rapid Rapid
Rhythm
Large
Pendular Pendular
Small Small OD/large OS Small Small
Pendular Pendular Pendular Pendular
Pattern R RV HV/roving VHR R Vr Hvr
Asymmetry U U U
+ + +
U
Initial Diagnosis
Diencephalic Syndrome Spasmus nutans Spasmus Spasmus Spasmus Spasmus
nutans nutans nutans nutans
y = year; m = months; M = male; F = female; U= unilateral only; B = bilateral only; U - B = started unilaterally and became bilateral; 00 = right eye; OS = left eye; R = primarily rotary; H = primarily horizontal; V = primarily vertical; HV, RV, VHR = equal components; v, r = lesser components vertical rotary; - = not stated; + = present.
also appeared to influence the presence of nystagmus. 12,13,16 It was seen in high frequency with chiasmal gliomas but rarely with purely optic nerve glioma. Our series further documents a common association between diencephalic syndrome of Russell and nystagmus. 18-28 In the cases of hypothalamic astrocytoma originally described by Russell, inanition occurred in young children with normal food intake. For example, Pelc l9 found nystagmus in all three of her patients with the diencephalic syndrome. In her literature review, she ascertained 18 of 29 cases (62%) with nystagmus and diencephalic syndrome. DeSousa et af' reported that half of their 12 cases with optochiasmatic glioma had nystagmus, all rotary; the average age at diagnosis was 1.1 years. In six often cases we studied, the nystagmus diminished or disappeared during the course of disease. This occurred . despite the poor visual outcome. Yet, in two others the nystagmus was unchanged. Four patients had persisting nystagmus on long-term follow-up. One with bilateral vertical, pendular nystagmus
at 4 months of age later developed "seesaw" nystagmus, decreased vision and bilateral optic atrophy by age 58 months. This history matches that of a similar patient described by Walsh and HOyt.29 "Seesaw" nystagmus is well-recognized in tumors of the parachiasmal region. 30 In another patient in our study, unilateral, slow pendular, wide-amplitude nystagmus eventually converted to the roving nystagmus presumably of blindness. She had no light perception and an amaurotic pupil in that eye. These ten cases reemphasize the importance of including intracranial tumor in the differential diagnosis when acquired nystagmus presents in infancy or early childhood. Since early neurologic and ophthalmologic examination may be otherwise normal, frequent followup is necessary. The presence of inanition, optic atrophy, papilledema or hydrocephalus will compel more extensive neurologic examination, including CT scan. Most often, the nystagmus was misdiagnosed as spasmus nutans and the eventual diagnosis of intracranial tumor was delayed. In virtually every case the nystagmus
Table 8. Literature Review of Acquired Nystagmus as a Presenting Sign of Intracranial Glioma of the Anterior Visual Pathways Tumor Involvement Author
Diagnosis
RON
LON
Chiasm
Udvarhelyi 1 Donin 2 Donin 2 Ciccarelli 3 Kelly4 Add y5 Schulman 6 Ant ony 7 Ant ony7 Koenig 8
Glioma, anaplastic Glioma Astrocytoma, grade II Astrocytoma OptiC glioma Astrocytoma, well differentiated Presumed optiC glioma Glioma Astrocytoma, low grade Astrocytoma, low grade
+ +
+
+ +
+ +
+ +
+ +
+ +
+ + + +
+ + + +
RON = right optiC nerve; LON = left optic nerve;
Hypothalamus
+
Other Third ventricle Third ventricle Third ventricle
+
+ = presence.
433
OPHTHALMOLOGY
•
MAY 1984
•
VOLUME 91
•
NUMBER 5
Table 9. Literature Review of Acquired Nystagmus as a Presenting Sign of Intracranial Glioma of the Anterior Visual Pathways Author Udvarhelyi' 00nin 2 Oonin 2 Ciccarelli 3 Kelly4 Add y5 Schulman 6 Ant ony 7 Ant ony 7 KoenigS
Head Nodding
Torticollis
+
Initial VA OO/OS
Initial Optic Atrophy OO/OS
Subsequent Optic Atrophy OO/OS
!GO> OS LOO/+F
+/+ +/+
-/-
+/+ +/+ +/+
-/-
+/+ +/+
-/-/-/-
+/+ +/+ +/+
LOU
+
-/+
+ + +
+ +
+F/+F +F/+F
Diencephalic Syndrome
+ +
Hydrocephal us + + + +
+
- = not stated; F = Fixation present; + = present; - = absent; 00 = right eye; OS = left eye; OU = both eyes. was asymmetric and pendular. When the nystagmus was of low frequency, it was more easily distinguished from the high-frequency oscillations of spasmus nutans.
ACKNOWLEDGMENT The authors acknowledge the following physicians for providing us access to their patient records: David G. Cogan, MD (Case 1); Mary K. Hammock, MD (Case 1 and 2); David F. Friendly, MD (Case 2); Neil R. Miller (Case 3); George L. Sheppard, MD (Case 3); Stephen Glass, MD (Case 5); Roger A. Niva, MD (Case 5); Paul E. Carlson, MD (Case 6); Robert Letson, MD (Case 6); Ray Truex, MD (Case 7 and 8); Boyd H. Seidenberg, MD (Case 9); Myles M. Behrens, MD (Case 9); Abe Chutorian, MD (Case 9); Joel Y. Rutman, MD (Case 10); Arthur E. Marlin, MD (Case 10); Stuart A. Terry, MD (Case 10).
10.
11 . 12. 13. 14. 15. 16. 17. 18.
REFERENCES
19. 20.
1. Udvarhelyi GB, Khodadoust AA, Walsh FB. Gliomas of the optic nerve and chiasm in children; an unusual series of cases. Clin Neurosurg 1965; 13:204-37. 2. Donin JF. Acquired monocular nystagmus in children. Can J Ophthalmol 1967; 2:212-5. 3. Ciccarelli EC, Huttenlocher PRoDiencephalic tumor. A cause of infantile nystagmus and cachexia. Arch Ophthalmol 1967; 78:350-3. 4. Kelly TW. Optic glioma presenting as spasmus nutans. Pediatrics 1970; 45:295-6. 5. Addy DP, Hudson FP. Diencephalic syndrome of infantile emaciation; analysis of literature and report of further 3 cases. Arch Dis Child 1972; 47:338-43. 6. Schulman JA, Shults WT, Jones JM Jr. Monocular vertical nystagmus as an initial sign of chiasmal glioma. Am J Ophthalmol 1979; 87:87-90. 7. Antony JH, Ouvrier RA, Wise G. Spasmus nutans: a mistaken identity. Arch Neurol 1980; 37:373-5. 8. Koenig SB, Naidich TP, Zaparackas Z . Optic glioma masquerading as spasmus nutans. J Pediatr Ophthalmol Strabismus 1982; 19:20-4. 9. O'Neill JF, Chu FC, Cogan DG, et al. Acquired nystagmus in infancy: a benign or threatening condition? Two case reports of Russell's diencephalic syndrome. In: Reinecke RD, ed. Strabismus II: Pro-
434
21 .
22. 23.
24. 25. 26. 27. 28. 29. 30.
ceedings of the International Strabismus Society. New York. Grune and Stratton, 1984. In press. Norton EWD, Cogan 00. Spasmus Nutans; a clinical study of twenty cases followed two years or more since onset. Arch Ophthalmol 1954; 52:442-6. Cogan 00. Congenital nystagmus. Can J Ophthalmol 1967; 2:4-10. Chutorian AM , Schwartz JF, Evans RA , Carter S. OptiC gliomas in children . Neurology 1964; 14:83- 95. Miller NR, Iliff WJ, Green WR. Evaluation and management of gliomas of the anterior visual pathways. Brain 1974; 97:743-54. Lloyd LA. Gliomas of the optic nerve and chiasm in childhood. Trans Am Ophthalmol Soc 1973; 71 :488-535. Walsh FB. The ocular signs of tumors involving the anterior visual pathways. Am J Ophthalmol 1956; 42:347-77. Dodge HW Jr, Love JG, Craig WM , et al. Gliomas of the optic nerve. Arch Neurol Psychiatr 1958; 79:607-21 . DeSousa AL, Kalsbeck JE, Mealey J Jr, et al. Optic chiasmatic glioma in Children. Am J Ophthalmol 1979; 87:376-81. Russell A. A diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 1951 ; 26:274. Pelc S. The diencephalic syndrome in infants; a review in relation to optic nerve glioma. Eur Neurol 1972; 7:321-34. Pelc S, Flament-Durand J. Histological evidence of optic chiasma glioma in the "diencephalic syndrome". Arch Neurol 1973; 28:139-40. DeSousa AL, Kalsbeck JE, Mealey J Jr, Fitzgerald J. Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases. Neurosurgery 1979; 4:207-9. Kagan H. Anorexia and severe inanition associated with a tumour involving the hypothalamus. Arch Dis Child 1958; 33:257-60. Braun FC Jr, Forney WR. Diencephalic syndrome of early infancy associated with brain tumor; report of a case and review of the literature. Pediatrics 1959; 24:609-15. Aas K. Diencephalic syndrome of emaciation; report of a case. Acta Paediatr 1963; 52:161-5. Hager A. The diencephalic syndrome of emaciation; a case report. Eur Neurol 1972; 7:130-5. Waga S, Shimizu T, Sakakura M. Diencephalic syndrome of emaciation (Russell's syndrome). Surg Neurol 1982; 17:141-6. Dads L. A diencephalic syndrome of early infancy. Med J Aust 1957; 44:689-91 . Dods L. A diencephalic syndrome of early infancy. Med J Aust 1967; 1:222-7. Walsh FB, Hoyt WF. Clinical Neuro-Ophthalmology, 3rd ed. Baltimore: Williams & Wilkins, 1969; 2092-3. Daroff RB. See-saw nystagmus. Neurology 1965; 15:874-7.
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Discussion by
Nancy M. Newman, MD The authors present a retrospective study of 10 patients with acquired nystagmus as a presenting sign of a chiasmal or parachiasmal glioma. Nine out often cases developed their nystagmus before 10 months of age. Frequently, the pendular and asymmetric nature ofthe nystagmus, combined with the age of onset, caused it to be titled "spasmus nutans." Following the onset of the nystagmus, an average of 8.4 months delay occurred before the correct diagnosis of an optic glioma was made; in those with spasmus nutans as a diagnosis, the delay was 14.5 months. This group of patients showed other problems, including optic atrophy which all of them eventually developed; the diencephalic syndrome was present in seven of the patients. The important point is made that an acquired nystagmus in childhood can be a harbinger of a life-threatening disease. It is interesting, as the authors point out, that none of these cases were misdiagnosed as congenital nystagmus. Perhaps the time of onset was a factor, as congenital nystagmus can be expected to be detected soon after birth; acquired nystagmus due to poor visual acuity usually has its onset before the 4 months of age; spasmus nutans usually presents in the latter half of the first year. The diencephalic syndrome, which is nearly pathognomonic of optic glioma, fortunately responds very well to radiation therapy, although the response of the glioma itself may be less impressive. Abnormal findings of the visual and oculomotor symptoms in infancy should not be glibly ascribed to a benign etiology. Any infant with oculomotor difficulties or optic atrophy deserves neuro-ophthalmic evaluation (with a careful look for nerve fiber layer changes, a Marcus-Gunn pupil, and visual field defects), neurological evaluation, and radiologic studies. It is unfortunate that the retrospective nature of the study did not allow for recording of head and eye movements, although these are difficult to do in an infant, because of the combination of head nodding, torticollis or head tilt, and asymmetrical, high frequency, pendular nystagmus that makes the diagnosis of spasmus nutans. There have been relatively few recordings of head and eye movements in true spasmus nutans. It would be of considerable interest to see whether there were any differences between those children with true spasmus nutans and these with optic gliomas. Gresty l.2 describes suppression of the nystagmus during head shaking in spasmus nutans, as opposed to congenital nystagmus who also have a decreased visual acuity and different wave forms from those of spasmus nutans. His patients with spasmus nutans had eye movements at a frequency of approximately II Hz and head movements at a frequency of 3 to 4 Hz. He also categorized three relationships between the head and eye move-
From the Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115.
ments: (I) the head tremor does not change the visual acuity or modify the nystagmus and may have the same origin as the oculomotor imbalance, (2) the head movement modifies the nystagmus in order to increase visual acuity; these two types of head/eye movement are found in congenital nystagmus, and (3) in spasmus nutans the head movement eliminates or suppresses the abnormal eye movements. Additionally, although none of the patients in this report were misdiagnosed as congenital nystagmus, recordings of head and eye movements may identify unusual wave forms and foveation strategy which are typical of congenital nystagmus and thus aid in differentiating it from spasmus nutans. The head nodding is usually a prominent part of the spasmus nutans triad of head nodding, torticollis, and asymmetrical nystagmus, and usually precedes the onset of the abnormal eye movement. Thus, the occurrence of an abnormal eye movement which could be spasmus nutans, but without the presence of head nodding, should lead one to suspect another cause such as the glioma which is found in these patients. As there are other masses which present in the region of the optic chiasm and hypothalamus, it is interesting that no other etiologies have been associated with this syndrome of pseudospasmus nutans or the diencephalic syndrome. This suggests that some age related factor is present in hypothalamic gliomas which is not seen with tumors that present later in childhood such as craniopharyngiomas. These latter tumors usually present with obesity, short stature, and abnormal eye movements, none of which are usually designated as spasmus nutans. Again, if the eye movements could have been recorded, it would be easier to compare them with those found in other modalities. A review of those cases presented reveals that if all three components were demanded for a diagnosis of spasmus nutans, and if no other neurologic abnormality (such as optic atrophy) are allowed, only one of the author's patients would have been diagnosed as having spasmus nutans. From the contents of this presentation, we should learn the specific lesson that an acquired nystagmus presenting in infancy, especially if it looks like spasmus nutans, may be the first sign ofa chiasmal glioma. Moreover, whenever a "benign" syndrome such as spasmus nutans presents without some of its typical components or with associated abnormal findings (such as the optic atrophy or diencephalic syndrome seen here), then it is incumbent upon us to thoroughly evaluate the patient for the possibility of a more threatening lesion. References 1. Gresty MA, Ell JJ. Spasmus nutans or congenital nystagmus? Classification according to objective criteria (Correspondence). Sr J Ophthalmol1981; 65:510-1. 2. Gresty M, Leech J, Saunders M, Eggars H. A study of head and eye movement in spasmus nutans. Sr J Ophthalmol 1976; 60:652- 4.
435
Abstract: This study is a multicenter, retrospective report of 10 infants in whom acquired nystagmus was the initial sign of chiasmalfparachiasmal glioma. Nine patients presented before the age of 10 months. The nystagmus, primarily described as pendular and asymmetric, was difficult to differentiate from and therefore most often diagnosed as spasmus nutans. On average in the ten patients, the intracranial glioma was not recognized for 8.6 months after the onset of nystagmus. In the five diagnosed as spasmus nutans, the mean delay in recognizing the tumor was 14.5 months. Three associated clinical findings were present or developed in these patients to distinguish this entity from spasmus nutans: optic atrophy in all ten patients, poor feeding due to diencephalic syndrome in 5 of 10, and increased intracranial pressure with hydrocephalus in 3 of 10. The acquired nystagmus in these infants was evidence of a life-threatening chiasmalfparachiasmal glioma. [Key words: acquired nystagmus, anterior visual pathway glioma, chiasmatic-optic nerve-hypothalamic astrocytoma, congenital nystagmus, diencephalic syndrome, spasmus nutans.] Ophthalmology 91 :425-435, 1984
Nystagmus in early childhood can present a diagnostic dilemma for the examining ophthalmologist. Because the majority of such cases are benign and unrelated to neurologic disease, attention has most often been drawn to distinguishing congenital nystagmus from spasmus nutans.
From The Wilmer Eye Institute. Johns Hopkins University Hospital, Baltimore, Maryland: the Department of Ophthalmology. Childrens Hospital National Medical Center. Washington, DC and Center for Sight, Georgetown University Medical Center. Washington, DC,t the National Eye Institutes, National Institutes of Health. Bethesda, Maryland,~ and the Department of Ophthalmology and Pediatrics, Temple University School of Medicine and SI. Christopher's Hospital for Children, Philadelphia.§ Presented at the Eighty-eighth Annual Meeting of the American Academy of Ophthalmology. Chicago, Illinois, October 30-November 3, 1983. Supported in part by a Heed-Richard G. Scobee Memorial Fellowship Grant and a National Children's Eye Care Foundation Research Award. Reprint requests to John F. O'Neill, MD, Department of Ophthalmology, Center for Sight, Georgetown University Medical Center, 3800 Reservoir Road NW, Washington, DC 20007.
Occasionally, acquired nystagmus in infancy has been the first sign of life-threatening chiasmal or parachiasmal gliomas. 1-8 The occurrence of these cases is rare, so careful evaluation of such children for associated ophthalmologic, neurologic, or systemic signs is important. This report analyzes the medical histories of ten patients from seven medical centers.
MATERIALS AND METHODS After reporting two cases of acquired infantile nystagmus with diencephalic syndrome due to intracranial glioma,9 we solicited similar cases from a number of major ophthalmic centers. Information was collected on a total of ten patients who met the criterion; acquired infantile nystagmus was the initial sign of intracranial glioma. Six of the ten were examined by one or more of the authors. Five other cases offered were not considered in the study because the nystagmus appeared as a late sign in the course of disease. 425
OPHTHALMOLOGY •
MAY 1984 •
VOLUME 91
•
NUMBER 5
Fig 1. Left. noncontrast cranial CT of case I at age 10 months demonstrating large, suprasellar hypolucent areas. Right. contrast enhancement revealing large, lobulated partially cystic hypothalamic astrocytoma.
Three case histories of acquired nystagmus were selected to highlight aspects of the disease process which led to further diagnostic workup: inanition, hydrocephalus, and optic atrophy.
CASE REPORTS Case 1. Acquired Nystagmus with Subsequent Inanition. At age 6 months a healthy girl was noted by the parents to have slow horizontal oscillations of her left eye; a similar pattern of movement began in the right eye I week later. The infant was the product of a full-term uncomplicated gestation and normal delivery with a birth weight of 8 Ibs, II oz. All growth and developmental milestones were appropriate and normal. During ophthalmological examination, asymmetrical nystagmus was noted and described as "slow, horizontal, pendular, and irregular." There was infrequent and irregular head nodding, but no deviation of the eyes or torticollis was observed. Good fixation and following movements and normal pupillary responses were present in each eye. The optic nerve heads showed no evidence of atrophy or papilledema. The provisional diagnosis was acquired nystagmus, probably spasmus nutans. Two weeks later the asymmetric slow horizontal nystagmus was still present with the addition of occasional small amplitUde vertical and torsional eye movements. Sporadic head nodding was still noted without torticollis. At the age of 8 months the
426
infant was seen at the National Eye Institute. Although the child's eyes were steady at times, horizontal conjugate pendular nystagmus was present, characterized by a frequency of I to 2 Hz and an amplitude of less than 50. Interspersed were bursts of smaller, vertical pendular oscillations which were intermittently conjugate and disconjugate. When disconjugate, the vertical movements were either similar to "seesaw" nystagmus, or one eye moved vertically while the other moved horizontally. Occasionally, oblique or circular oscillations were noted. Head nodding was infrequent and did not appear to be correlated with the eye movements. The pattern of nystagmus was unlike that in spasmus nutans because of its relatively low frequency of oscillations, and unlike that in congenital nystagmus because of its irregular pendular pattern. During this examination, the additional history of irritability, ambivalence to feeding and weight stabilization was obtained. It was recommended that the child undergo further neurological studies and CT scanning. Several weeks elapsed while the family was reluctant to have the child studied radiologically. At 9 112 months a neurologist found her to be normal except for slight hypotonia with hyperreflexia of the lower extremities. The infant began to lose weight and at age 10 months cranial CT scan demonstrated a large, intrinsic, partially cystic intracranial mass in the hypothalamic area (Fig I). Angiography demonstrated displacement of the cerebral arterial system bilaterally, and confirmed the presence of a suprasellar mass. Right frontal craniotomy revealed an encapsulated chiasmatic/hypothalamic lesion infiltrating the right optic nerve and displacing the left. Histopathologic di-
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Fig 2. Left, bilateral optic atrophy in case I at age 22 months, greater in the right eye than in the left eye (right).
agnosis was low-grade astrocytoma. A total of 4500 rad was administered over a 4-week period beginning 2 weeks postoperatively. At 22 months follow-up the child enjoyed good general health with increased appetite, good food intake, and progressive weight gain. Although the nystagmus was diminished, bilateral optic atrophy developed which was greater in the right eye. (Fig 2) There was an increasing esotropia with poor abduction of both eyes. (Fig 3) She underwent recession of both medial rectus muscles at age 2 years.
nystagmus. There was decreased vision of the right eye and right exotropia along with bilateral optic nerve pallor, greater on the right. At age 32 months, four small cafe-au-Iait spots were noted but were not considered sufficient to justify a diagnosis of neurofibromatosis. The most recent ophthalmologic exam at age 45 months noted a decrease in the nystagmus. The right eye has eccentric fixation, exotropia, and marked optic atrophy, and left eye central, unsteady maintained fixation and moderate
COMMENT
Pendular asymmetric nystagmus was the presenting sign of an intracranial glioma. When signs of the diencephalic syndrome became apparent, CT scan disclosed a tumor involving both the optic chiasm and hypothalamus. Although the tumor resolved following radiation therapy, bilateral optic atrophy developed. Case 5. Acquired Nystagmus with Subsequent Papilledema. A 3-month, l-week-old girl was noted by the parents to have the onset of nystagmus in her left eye only. The infant was the product of an uncomplicated full-term gestation and delivery. Development had progressed normally. Examination the following week by a pediatric ophthalmologist disclosed a bilateral small-amplitude high-frequency horizontal nystagmus which was greater in the right eye. Good fixation was obtained in the right eye but only central unsteady fixation in the left. The pupillary responses and posterior poles were normal. The diagnosis was spasmus nutans. On reexamination I week later, the patient was noted to have papilledema. CT scan demonstrated a large spherical 5-cm contrast-enhancing mass extending from the sella to the level of the foramen of Monroe. At craniotomy, the tumor was found to arise from the chiasm and extend into the left optic nerve and the hypothalamus. The tumor was biopsied, the left orbit decompressed, and bilateral subdural-peritoneal shunts inserted. Histopathologic diagnosis was astrocytoma, Grade II. A course of radiation therapy totalling 4500 rad was delivered to the tumor field. At age 10 months the patient developed left-sided weakness secondary to a right cerebrovascular accident. At age 24 months a single seizure occurred and on ophthalmologic exam there was persistence of pendular, small amplitude, rapid, horizontal
Fig 3. Progressive esotropia in case I at 22 months of age here at II months after craniotomy and 10 months after completion of radiation therapy.
427
OPHTHALMOLOGY
•
MAY 1984
•
VOLUME 91
•
NUMBER 5
Table 1. Characteristics of Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathway
Case No.
2 3 4 5 6 7
8
9
10
Age of Onset of Nystagmus (months)
Sex
Unilateral or Bilateral
6
F
5 5% 5 3114 23 7213
M M M F M M F F M
9
4
93/.1
Frequency
Amplitude
Rhythm
Pattern
Asymmetry
U----B
Slow
Small
Pendular
Hvoc
+
Variable
U B U-B U-B U-B U U U-B U-B
Slow Rapid
Moderate
U
Rapid
Small
H Hvot Hvct H
+ + +
U Conjugate Conjugate
Slow
Large Small
U U
U U
Rapid
Small
Mixed Pendular Pendular Pendular Pendular Pendular Pendular
V H Vr H
+ +
Conjugacy
Initial Diagnosis Acq. nyst., possibly spasmus nutans Diencephalic syndrome Acq. nyst. Spasmus nutans Spasmus nutans Acq. nyst. and O.A. Acq. nyst. and OA Acq. nyst. and O.A. Spasmus nutans Spasmus nutans
M = male; F = female; U = unilateral only; B = bilateral only; U ---+ B = started unilateral and became bilateral; H = primarily horizontal; v, 0, c, r, t = lesser components of vertical, oblique, circular, rotary, or torsional nystagmus; V = primarily vertical; Acq. nyst. = acquired nystagmus; OA = optic atrophy.; - = not stated.
optic atrophy. CT scan at age 49 months revealed no evidence of residual tumor. The patient has delayed mental development. COMMENT
This case demonstrates rapid asymmetric pendular nystagmus highly suggestive of spasmus nutans as the presenting sign of intracranial glioma. Although the fundi were initially normal, papilledema was noted the following week. At the time of tumor, biopsy shunting procedures were necessary and shortly thereafter radiation treatment was given. The subsequent course included bilateral optic atrophy with decreased vision. Case 8. Acquired Nystagmus and Optic Atrophy. This 9-month-old girl presented with a 2-week history of unilateral nystagmus and intermittent exodeviation of the right eye. The patient was well-developed, well-nourished and had a normal gestation, delivery and perinatal period. There was no family history of nystagmus or neurofibromatosis. Examination revealed good fixation of the left eye, but no fixation of the right could be elicited. Both pupils reacted well to light. There was a fine unilateral horizontal pendular nystagmus of the right eye. Neither head nodding nor torticollis were present but there was an intermittent variable right exotropia. The maculae were normal. The left optic nerve head was normal. However, equivocal pallor and flattening of the right optic disc prompted further neurological workup. CT scan demonstrated an intensely enhancing solid tumor measuring up to 24 mm in diameter, situated above the planum sphenoidale and filling the sella turcica. There was no evidence of hydrocephalus. Cerebral angiography confirmed the presence of an avascular, suprasellar mass. Curiously, the monocular nystagmus in the right eye ceased on the day prior to surgical intervention. Surgery revealed that the large tumor involved the optic chiasm, the right optic nerve and tract, and left optic nerve. Subtotal resection was performed. The histopathologic diagnosis was astrocytoma Grade I or II. A right afferent pupillary defect was detected immediately postoperatively. Vincristine and Actinomycin D were administered.
428
In the follow-up examination 1 month later, nystagmus was not present. Visual response in the right eye to large objects was obtained just in the infero-temporal field. The left eye had good fixation. Pupillary reaction to light in the right eye was decreased and the left eye was normal. The right optic disc was slightly pale, the left optic disc was normal. There was a 25prism diopter right exotropia. CT scan at age 13 months showed a decrease in the extent of the tumor with the presence of cysts within the tumor. COMMENT
Acquired uniocular nystagmus and minimal optic atrophy were the presenting signs of intracranial tumor. No other localizing neurologic signs or symptoms were' present. Interestingly, the nystagmus in the right eye was transitory and ceased prior to surgical or chemotherapeutic intervention.
RESULTS With the exception of one patient, the onset of nystagmus occurred before the age of 10 months (Table 1). In nine of ten patients, the nystagmus was initially unilateral; one patient had bilateral nystagmus from the onset. Of the unilateral cases, six eventually manifested bilateral nystagmus. Throughout the course of observation, the nystagmus remained unilateral in the other three patients. In the majority of the cases, the nystagmus was pendular and asymmetric. It was purely pendular in seven patients, and mixed pendular/jerk in one patient. No patient had isolated jerk nystagmus. In the bilateral cases where the comparison was made, asymmetry was noted. Three other cases were unilateral, which by definition would be asymmetric. Several other characteristics ofthe nystagmus were less consistent. Horizontal nystagmus was prominent, but
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Table 2. Ophthalmic Findings at Presentation in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No.
Head Nodding
1 2 3 4 5 6 7 8 9 10
+
Torticollis +
+ +
+ +
+
Vision OD/OS +F/+F +F/+F +F/+F +F/+F C?SM/U !V/lV no F/+F no F/+F +F/+F +F/+F
Optic Atrophy OD/OS
-/-
-/?/?
-/-
+/+ +/+/-
-/-/-
Pupillary Reactions nl nl nl nl nl nl !OD/nIOS nl nl nl
Afferent Pupillary Defect
None
+00
Strabismus
Neurofibromatosis
Family History of Nystagmus
X(T)OD
X(T)OD +
+ = present; - = not present; - = not stated; 00 = right eye; OS = left eye; F = Fixation; C?SM = central, questionable steadiness, maintained fixation; U = unsteady fixation; !V = decreased vision; ?/? = questionably pale disks OU; nl = normal; X(T) = intermittent exotropia.
variable degrees of vertical, oblique, circular, or torsional nystagmus were also described in three patients. Two other patients had primarily vertical nystagmus, involving one eye in one patient, and both eyes in the other. Where recorded, the nystagmus was most often of small amplitude (four of six patients), but one patient had moderateamplitude and another had wide-amplitude nystagmus. The frequency was rapid in three cases and slow in three others. Head nodding, torticollis, or both were present in six of ten cases (Table 2). Spasmus nutans was diagnosed in five cases and these were followed for 1 week to 41f2 years before a second sign prompted further neurologic studies. Initially, normal fixation was present in six of ten patients. Four others had decreased vision, either unilaterally or bilaterally. In only one case was an afferent pupillary defect seen. Initially, nine of ten cases had normal pupillary responses. Strabismus was present in two cases and subsequently developed in five others. Optic atrophy was initially present in only three cases, unilateral in two patients, and bilateral in one. When optic atrophy was
observed, this finding resulted in further investigation for intracranial tumor. The interval between onset of nystagmus and diagnosis of glioma ranged from 15 days to 54 months (average, 8.6 months). In the five patients discussed as spasmus nutans, the average delay in recognition of the glioma was 14.5 months. The delay in one case of 6 months could be attributed in part to a strong family history of nystagmus (maternal grandmother, maternal great uncle) and a history of head nodding in the fraternal twin. None of the patients had neurofibromatosis. One case had four small cafe-au-Iait spots, but these were deemed insufficient evidence to establish a diagnosis of neurofibromatosis. In eight cases, no evidence for neurofibromatosis in the family history could be found. Two associated systemic conditions commonly occurred which necessitated further workup: diencephalic syndrome and hydrocephalus (Table 3). Diencephalic syndrome was recognized in one-half of the cases, the earliest concurrently with presentation, the latest 9 months after the onset of nystagmus. One patient developed pap-
Table 3. Systemic Findings in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Age of Onset of Nystagmus (months)
Case No.
6 5 5V2 5 3% 23
1 2 3 4 5 6 7 8 9 10 +
7213 9% 4 93/.1
=
present; -
=
Second Sign or Symptom
Age at second Sign/Symptoms (months)
Poor feeding Poor feeding Optic atrophy & hydrocephalus Poor feeding Papilledema & hydrocephalus Optic atrophy Poor feeding Optic atrophy Optic atrophy Poor feeding
8 10 25 6% 3% 28 7213 10 58 15
not present.
Diencephalic Syndrome + + +
Hydrocephalus
+ +
+
+
+
+
Age at Tumor Diagnosis (months)
Interval from Onset of Nystagmus to Tumor Diagnosis (months)
10 10 6 10 4% 29 8213 10% 58· 18
4 5 % 5 1% 6 1 1% 54 8%
• Presumed optic glioma.
429
OPHTHALMOLOGY
•
MAY 1984 •
VOLUME 91
•
NUMBER 5
Table 4. Extent of Tumor Involvement in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No.
Diagnosis
Biopsy proven
1 2 3
Astrocytoma, low grade Astrocytoma, grade II Astrocytoma, grade II
yes yes yes
4 5
Optic glioma, grade I Astrocytoma, grade II Optic glioma Astrocytoma, grade I Astrocytoma, grade I-II Presumed optic glioma Astrocytoma, grade II
yes yes yes yes yes no yes
6
7 8
9
10
Tumor Involvement RON
LON
Chiasm
Hypothalmus
+
+"
+
+
+ + +
+ + +
+
+ + +
+ + + + + + +
+ +
+ + + + +
+ + +
Other
Right frontal and temporal lobes, thalamus; later ascites ftuid.
+
Right optic tract Right & Left optic tracts, midbrain, diffuse subarachnoid nodules, cerebellum, spinal cord; ablation of the pituitary gland 20 to radiation (autopsy).
+
RON = right optic nerve; LON = left optic nerve; + = present. " Optic nerve displaced laterally.
illedema as evidence for hydrocephalus 2 weeks after onset of the nystagmus. Three other patients developed hydrocephalus during their course of follow-up after tumor diagnosis. A diagnosis of intracranial glioma was established in all ten of these patients (Table 4). In nine it was histopathologically proven, with eight classified as low grade. All ten had demonstrable optic chiasmatic involvement. Where the hypothalamus was affected, diencephalic syndrome or hydrocephalus was invariably present. Follow-up after tumor diagnosis of the glioma (Table 5) averaged 48.5 months (range, 4-69 months). Radiation therapy to the site of the tumor was administered in nine of ten patients. Three patients received chemotherapy. The nystagmus disappeared in three patients, decreased
in three and was unchanged in two others. In another patient, it converted to unilateral roving nystagmus. In one patient examined at age 58 months, CT scan revealed "seesaw" nystagmus and optic atrophy with enlargement of the optic chiasm and both optic nerves. On follow-up CT (Table 6), one case showed complete resolution of tumor while four showed a decreased tumor size (Fig 4). No change was seen in two cases while tumor enlargement occurred in three cases. Nevertheless, all 10 cases developed progressive optic atrophy. On follow-up, an afferent pupillary defect was recorded in eight of ten cases. Four of five patients with diencephalic syndrome improved after radiation therapy; one patient had recurrent inanition when tumor growth recurred. Two patients fol-
Table 5. Ophthalmologic Outcome in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No. 1 2 3 4 5
6 7
8
9
10
Therapy Radiation 4500 r Radiation 4500 r Radiation 5040 r & chemotherapy Radiation 4000 r Radiation 4500 r Radiation 5550 r Radiation 4500 r & chemotherapy Chemotherapy Radiation 4500 r Radiation 5000 r
Follow-up (months)
Nystagmus
Vision
Afferent Pupillary Defect
Optic Atrophy
Strabismus
+OD +OD
OD> OD OD> OS OD> OS
ET OS XT OD X(T)OD
66
42
Decreased Ceased Decreased
Poor F; +F 5/400, 20/25 3/200; 8/200
154 42
Continued Decreased
NLP; NLP Eccentric; central unsteady 20/30; HM NLP; 20/30
OU amaurotic
OU OD> OS
XT OD
+OS OD amaurotic
OD> OD OD> OS
X(T)OD
Peripheral field; +F Unsteady; 20/80 NPL; 20/400
+OD +OD OD amaurotic
OD only OD> OS OD> OS
22
51 27 4 8
69"
Ceased Continued OD roving Ceased Seesaw OD > OS Continued
XT OD None
r = rad; F = fixation; NLP = no light perception; HM = hand motion; ET = esotropia; XT = exotropia; X(T) = intermittent exotropia; OD = right eye; OS = left eye; OU = both eyes; - = not stated. " Died at 7 yrs, 3 mos.
430
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Table 6. Medical Outcome in Acquired Nystagmus due to Intracranial Glioma of the Anterior Visual Pathways in Early Childhood Case No. 1 2 3
Follow-up (months)
Therapy
Shrinkage Dramatic shrinkage Enlargement at age 25 mo. No change Complete resolution
Resolived Resolved None
+
Resolved None
+
4 5
6
Radiation 5550 r
51
Shrinkage
None
7
Radiation 4500 r & Chemotherapy
27
Resolved
8
Chemotherapy Radiation 4500 r Radiation 5000 r
Initial shrinkage; age 70 mo; enlargement Shrinkage No change Enlargement, then extension & diffuse CNS seeding
10
r = rad; n = normal; GH " Died age 7 yrs, 3 mos.
66
42
154 42
4
8
69"
=
CSF Shunt Procedure(s)
Inanition
Radiation 4500 r Radiation 4500 r Radiation 5040 r & Chemotherapy Radiation 4000 r Radiation 4500 r
9
22
CT Tumor Response
growth hromone; R = right; CVA
=
lowed for more than 5 years developed growth hormone deficiency. One of these also had adrenal insufficiency and diabetes insipidus 1 year before dying from progressive hydrocephalus, mental deterioration, and shunt infection.
DISCUSSION We have reviewed records of ten patients, from seven centers, with acquired nystagmus as the first sign of an intracranial glioma. Nine of ten patients were less than 10 months of age when the nystagmus was first observed; the remaining patient was 23 months of age. The nystagmus was typically pendular and asymmetric. In nine of ten patients the nystagmus was unilateral initially; in six it became bilateral, while in three it remained unilateral. The nystagmus was horizontal in seven of nine cases. But there were episodes of vertical, oblique, torsional, or circular nystagmus in three patients and two patients had primarily vertical nystagmus. Six patients had associated headnodding, torticollis, or both. The acquired nystagmus seen in this condition must be distinguished principally from spasmus nutans, a benign condition with asymmetric nystagmus, head nodding and torticollis,IO and from congenital nystagmus. It was impressive that five of the ten patients in our series were initially diagnosed as having spasmus nutans, leading to a delay in recognition of the intracranial tumor for an average 14.5 months. The nystagmus and head nodding in patients with the gliomas were similar to that in spasmus nutans. The onset of nystagmus in both conditions most often occurs prior
Neurologic Status
n GH deficit
Mental retardation
n n
+
None None Improved, then recurred
cerebrovascular;
Endocrine Status
+
Small stature n n GH deficit, Adrenal insufficiency Diabetes insipidus
+
=
present; -
=
not present; -
=
Mental retardation R CVA, seizures, Mental retardation R hemiparesis n intellect n n n Progressive hydrocephalus, infection, death
not siated.
to age one year. IO The description of rapid, fine asymmetric nystagmus in two of our cases with gliomas was similar to that of spasmus nutans. The finding of both head nodding and torticollis in one of these patients made the distinction from spasmus nutans especially difficult. Finally, as in spasmus nutans, the nystagmus in six of our ten cases decreased or resolved in follow-up. Interestingly, none of the cases we reviewed were labelled congenital nystagmus, which would be typically recognized as being horizontal, conjugate and relatively regular, whether jerk or pendular. II One of our cases was diagnosed as spasmus nutans despite a strong family history of nystagmus. Tables 7 through 9 summarize ten previous case reports where acquired infantile nystagmus was the initial sign of an intracranial tumor. I-8 There were striking parallels between the summaries of those reports and our observations. Spasmus nutans was the initial diagnosis in half of those reports. The onset of nystagmus ranged from 1 to 36 months; seven of ten were age 12 months or less. Where stated, the nystagmus was described as pendular and asymmetric. Five of those 10 cases had rapid frequency nystagmus. Head nodding, torticollis or both were described in half of the previous reports. Other similarities included the diagnosis of low-grade chiasmal glioma, relatively infrequent optic atrophy on the initial visit (three of eight cases), and tumor involvement of one or both optic nerves (eight of ten cases). In other studies of anterior visual pathway gliomas l2 - 17 the frequency of nystagmus in patients with chiasmatic gliomas ranged from 9 to 42%. Chutorian et al 12 specifically mentioned nystagmus as an initial sign in 8 of their
431
OPHTHALMOLOGY •
MAY 1984 •
VOLUME 91
•
NUMBER 5
Fig 4. Top left, contrast-enhanced cr scan of case 2 at age II months, showing a large cystic hypothalamic astrocytoma prior to radiation therapy. Top right, marked reduction in tumor size after completion of radiation ' therapy (4500R). Bottom left, complete resolution of hypothalamic tumor shown on contrast-enhanced cr 3 years after radiation therapy.
13 patients with chiasmal gliomas. It was also clear that the occurrence of nystagmus in chiasmatic gliomas was age-dependent; it was seen mainly in younger children. The best delineation of such a relationship was the study
432
of Miller et alY In the patients aged 6 years or less, 8 of 21 developed nystagmus, 4 ofthese 8 were younger than 1 year of age. In contrast, no patients 10 years of age or older had nystagmus. The anatomic location of the glioma
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Table 7. literature Review of Acquired Nystagmus as a Presenting Sign of Intracranial Glioma of the Anterior Visual Pathway
Author
Age of onset of Nystagmus
Sex
Udvarhelyi 1 Donin 2 Donin2 Ciccarelli 3 Kellt Add y5 Schulman 6 Ant ony 7 Ant ony 7 Koenig 8
3y 31 m 7m 1m 8m 5m 3y 13 m 10 m 4m
M M M M M F M F M F
Unilateral or Bilateral
Amplitude
Frequency
U U U B B U-B U-B U-B U
8
Rapid Rapid Slow Rapid Rapid Rapid
Rhythm
Large
Pendular Pendular
Small Small OD/large OS Small Small
Pendular Pendular Pendular Pendular
Pattern R RV HV/roving VHR R Vr Hvr
Asymmetry U U U
+ + +
U
Initial Diagnosis
Diencephalic Syndrome Spasmus nutans Spasmus Spasmus Spasmus Spasmus
nutans nutans nutans nutans
y = year; m = months; M = male; F = female; U= unilateral only; B = bilateral only; U - B = started unilaterally and became bilateral; 00 = right eye; OS = left eye; R = primarily rotary; H = primarily horizontal; V = primarily vertical; HV, RV, VHR = equal components; v, r = lesser components vertical rotary; - = not stated; + = present.
also appeared to influence the presence of nystagmus. 12,13,16 It was seen in high frequency with chiasmal gliomas but rarely with purely optic nerve glioma. Our series further documents a common association between diencephalic syndrome of Russell and nystagmus. 18-28 In the cases of hypothalamic astrocytoma originally described by Russell, inanition occurred in young children with normal food intake. For example, Pelc l9 found nystagmus in all three of her patients with the diencephalic syndrome. In her literature review, she ascertained 18 of 29 cases (62%) with nystagmus and diencephalic syndrome. DeSousa et af' reported that half of their 12 cases with optochiasmatic glioma had nystagmus, all rotary; the average age at diagnosis was 1.1 years. In six often cases we studied, the nystagmus diminished or disappeared during the course of disease. This occurred . despite the poor visual outcome. Yet, in two others the nystagmus was unchanged. Four patients had persisting nystagmus on long-term follow-up. One with bilateral vertical, pendular nystagmus
at 4 months of age later developed "seesaw" nystagmus, decreased vision and bilateral optic atrophy by age 58 months. This history matches that of a similar patient described by Walsh and HOyt.29 "Seesaw" nystagmus is well-recognized in tumors of the parachiasmal region. 30 In another patient in our study, unilateral, slow pendular, wide-amplitude nystagmus eventually converted to the roving nystagmus presumably of blindness. She had no light perception and an amaurotic pupil in that eye. These ten cases reemphasize the importance of including intracranial tumor in the differential diagnosis when acquired nystagmus presents in infancy or early childhood. Since early neurologic and ophthalmologic examination may be otherwise normal, frequent followup is necessary. The presence of inanition, optic atrophy, papilledema or hydrocephalus will compel more extensive neurologic examination, including CT scan. Most often, the nystagmus was misdiagnosed as spasmus nutans and the eventual diagnosis of intracranial tumor was delayed. In virtually every case the nystagmus
Table 8. Literature Review of Acquired Nystagmus as a Presenting Sign of Intracranial Glioma of the Anterior Visual Pathways Tumor Involvement Author
Diagnosis
RON
LON
Chiasm
Udvarhelyi 1 Donin 2 Donin 2 Ciccarelli 3 Kelly4 Add y5 Schulman 6 Ant ony 7 Ant ony7 Koenig 8
Glioma, anaplastic Glioma Astrocytoma, grade II Astrocytoma OptiC glioma Astrocytoma, well differentiated Presumed optiC glioma Glioma Astrocytoma, low grade Astrocytoma, low grade
+ +
+
+ +
+ +
+ +
+ +
+ +
+ + + +
+ + + +
RON = right optiC nerve; LON = left optic nerve;
Hypothalamus
+
Other Third ventricle Third ventricle Third ventricle
+
+ = presence.
433
OPHTHALMOLOGY
•
MAY 1984
•
VOLUME 91
•
NUMBER 5
Table 9. Literature Review of Acquired Nystagmus as a Presenting Sign of Intracranial Glioma of the Anterior Visual Pathways Author Udvarhelyi' 00nin 2 Oonin 2 Ciccarelli 3 Kelly4 Add y5 Schulman 6 Ant ony 7 Ant ony 7 KoenigS
Head Nodding
Torticollis
+
Initial VA OO/OS
Initial Optic Atrophy OO/OS
Subsequent Optic Atrophy OO/OS
!GO> OS LOO/+F
+/+ +/+
-/-
+/+ +/+ +/+
-/-
+/+ +/+
-/-/-/-
+/+ +/+ +/+
LOU
+
-/+
+ + +
+ +
+F/+F +F/+F
Diencephalic Syndrome
+ +
Hydrocephal us + + + +
+
- = not stated; F = Fixation present; + = present; - = absent; 00 = right eye; OS = left eye; OU = both eyes. was asymmetric and pendular. When the nystagmus was of low frequency, it was more easily distinguished from the high-frequency oscillations of spasmus nutans.
ACKNOWLEDGMENT The authors acknowledge the following physicians for providing us access to their patient records: David G. Cogan, MD (Case 1); Mary K. Hammock, MD (Case 1 and 2); David F. Friendly, MD (Case 2); Neil R. Miller (Case 3); George L. Sheppard, MD (Case 3); Stephen Glass, MD (Case 5); Roger A. Niva, MD (Case 5); Paul E. Carlson, MD (Case 6); Robert Letson, MD (Case 6); Ray Truex, MD (Case 7 and 8); Boyd H. Seidenberg, MD (Case 9); Myles M. Behrens, MD (Case 9); Abe Chutorian, MD (Case 9); Joel Y. Rutman, MD (Case 10); Arthur E. Marlin, MD (Case 10); Stuart A. Terry, MD (Case 10).
10.
11 . 12. 13. 14. 15. 16. 17. 18.
REFERENCES
19. 20.
1. Udvarhelyi GB, Khodadoust AA, Walsh FB. Gliomas of the optic nerve and chiasm in children; an unusual series of cases. Clin Neurosurg 1965; 13:204-37. 2. Donin JF. Acquired monocular nystagmus in children. Can J Ophthalmol 1967; 2:212-5. 3. Ciccarelli EC, Huttenlocher PRoDiencephalic tumor. A cause of infantile nystagmus and cachexia. Arch Ophthalmol 1967; 78:350-3. 4. Kelly TW. Optic glioma presenting as spasmus nutans. Pediatrics 1970; 45:295-6. 5. Addy DP, Hudson FP. Diencephalic syndrome of infantile emaciation; analysis of literature and report of further 3 cases. Arch Dis Child 1972; 47:338-43. 6. Schulman JA, Shults WT, Jones JM Jr. Monocular vertical nystagmus as an initial sign of chiasmal glioma. Am J Ophthalmol 1979; 87:87-90. 7. Antony JH, Ouvrier RA, Wise G. Spasmus nutans: a mistaken identity. Arch Neurol 1980; 37:373-5. 8. Koenig SB, Naidich TP, Zaparackas Z . Optic glioma masquerading as spasmus nutans. J Pediatr Ophthalmol Strabismus 1982; 19:20-4. 9. O'Neill JF, Chu FC, Cogan DG, et al. Acquired nystagmus in infancy: a benign or threatening condition? Two case reports of Russell's diencephalic syndrome. In: Reinecke RD, ed. Strabismus II: Pro-
434
21 .
22. 23.
24. 25. 26. 27. 28. 29. 30.
ceedings of the International Strabismus Society. New York. Grune and Stratton, 1984. In press. Norton EWD, Cogan 00. Spasmus Nutans; a clinical study of twenty cases followed two years or more since onset. Arch Ophthalmol 1954; 52:442-6. Cogan 00. Congenital nystagmus. Can J Ophthalmol 1967; 2:4-10. Chutorian AM , Schwartz JF, Evans RA , Carter S. OptiC gliomas in children . Neurology 1964; 14:83- 95. Miller NR, Iliff WJ, Green WR. Evaluation and management of gliomas of the anterior visual pathways. Brain 1974; 97:743-54. Lloyd LA. Gliomas of the optic nerve and chiasm in childhood. Trans Am Ophthalmol Soc 1973; 71 :488-535. Walsh FB. The ocular signs of tumors involving the anterior visual pathways. Am J Ophthalmol 1956; 42:347-77. Dodge HW Jr, Love JG, Craig WM , et al. Gliomas of the optic nerve. Arch Neurol Psychiatr 1958; 79:607-21 . DeSousa AL, Kalsbeck JE, Mealey J Jr, et al. Optic chiasmatic glioma in Children. Am J Ophthalmol 1979; 87:376-81. Russell A. A diencephalic syndrome of emaciation in infancy and childhood. Arch Dis Child 1951 ; 26:274. Pelc S. The diencephalic syndrome in infants; a review in relation to optic nerve glioma. Eur Neurol 1972; 7:321-34. Pelc S, Flament-Durand J. Histological evidence of optic chiasma glioma in the "diencephalic syndrome". Arch Neurol 1973; 28:139-40. DeSousa AL, Kalsbeck JE, Mealey J Jr, Fitzgerald J. Diencephalic syndrome and its relation to opticochiasmatic glioma: review of twelve cases. Neurosurgery 1979; 4:207-9. Kagan H. Anorexia and severe inanition associated with a tumour involving the hypothalamus. Arch Dis Child 1958; 33:257-60. Braun FC Jr, Forney WR. Diencephalic syndrome of early infancy associated with brain tumor; report of a case and review of the literature. Pediatrics 1959; 24:609-15. Aas K. Diencephalic syndrome of emaciation; report of a case. Acta Paediatr 1963; 52:161-5. Hager A. The diencephalic syndrome of emaciation; a case report. Eur Neurol 1972; 7:130-5. Waga S, Shimizu T, Sakakura M. Diencephalic syndrome of emaciation (Russell's syndrome). Surg Neurol 1982; 17:141-6. Dads L. A diencephalic syndrome of early infancy. Med J Aust 1957; 44:689-91 . Dods L. A diencephalic syndrome of early infancy. Med J Aust 1967; 1:222-7. Walsh FB, Hoyt WF. Clinical Neuro-Ophthalmology, 3rd ed. Baltimore: Williams & Wilkins, 1969; 2092-3. Daroff RB. See-saw nystagmus. Neurology 1965; 15:874-7.
LAVERY, et al
•
ACQUIRED NYSTAGMUS
Discussion by
Nancy M. Newman, MD The authors present a retrospective study of 10 patients with acquired nystagmus as a presenting sign of a chiasmal or parachiasmal glioma. Nine out often cases developed their nystagmus before 10 months of age. Frequently, the pendular and asymmetric nature ofthe nystagmus, combined with the age of onset, caused it to be titled "spasmus nutans." Following the onset of the nystagmus, an average of 8.4 months delay occurred before the correct diagnosis of an optic glioma was made; in those with spasmus nutans as a diagnosis, the delay was 14.5 months. This group of patients showed other problems, including optic atrophy which all of them eventually developed; the diencephalic syndrome was present in seven of the patients. The important point is made that an acquired nystagmus in childhood can be a harbinger of a life-threatening disease. It is interesting, as the authors point out, that none of these cases were misdiagnosed as congenital nystagmus. Perhaps the time of onset was a factor, as congenital nystagmus can be expected to be detected soon after birth; acquired nystagmus due to poor visual acuity usually has its onset before the 4 months of age; spasmus nutans usually presents in the latter half of the first year. The diencephalic syndrome, which is nearly pathognomonic of optic glioma, fortunately responds very well to radiation therapy, although the response of the glioma itself may be less impressive. Abnormal findings of the visual and oculomotor symptoms in infancy should not be glibly ascribed to a benign etiology. Any infant with oculomotor difficulties or optic atrophy deserves neuro-ophthalmic evaluation (with a careful look for nerve fiber layer changes, a Marcus-Gunn pupil, and visual field defects), neurological evaluation, and radiologic studies. It is unfortunate that the retrospective nature of the study did not allow for recording of head and eye movements, although these are difficult to do in an infant, because of the combination of head nodding, torticollis or head tilt, and asymmetrical, high frequency, pendular nystagmus that makes the diagnosis of spasmus nutans. There have been relatively few recordings of head and eye movements in true spasmus nutans. It would be of considerable interest to see whether there were any differences between those children with true spasmus nutans and these with optic gliomas. Gresty l.2 describes suppression of the nystagmus during head shaking in spasmus nutans, as opposed to congenital nystagmus who also have a decreased visual acuity and different wave forms from those of spasmus nutans. His patients with spasmus nutans had eye movements at a frequency of approximately II Hz and head movements at a frequency of 3 to 4 Hz. He also categorized three relationships between the head and eye move-
From the Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115.
ments: (I) the head tremor does not change the visual acuity or modify the nystagmus and may have the same origin as the oculomotor imbalance, (2) the head movement modifies the nystagmus in order to increase visual acuity; these two types of head/eye movement are found in congenital nystagmus, and (3) in spasmus nutans the head movement eliminates or suppresses the abnormal eye movements. Additionally, although none of the patients in this report were misdiagnosed as congenital nystagmus, recordings of head and eye movements may identify unusual wave forms and foveation strategy which are typical of congenital nystagmus and thus aid in differentiating it from spasmus nutans. The head nodding is usually a prominent part of the spasmus nutans triad of head nodding, torticollis, and asymmetrical nystagmus, and usually precedes the onset of the abnormal eye movement. Thus, the occurrence of an abnormal eye movement which could be spasmus nutans, but without the presence of head nodding, should lead one to suspect another cause such as the glioma which is found in these patients. As there are other masses which present in the region of the optic chiasm and hypothalamus, it is interesting that no other etiologies have been associated with this syndrome of pseudospasmus nutans or the diencephalic syndrome. This suggests that some age related factor is present in hypothalamic gliomas which is not seen with tumors that present later in childhood such as craniopharyngiomas. These latter tumors usually present with obesity, short stature, and abnormal eye movements, none of which are usually designated as spasmus nutans. Again, if the eye movements could have been recorded, it would be easier to compare them with those found in other modalities. A review of those cases presented reveals that if all three components were demanded for a diagnosis of spasmus nutans, and if no other neurologic abnormality (such as optic atrophy) are allowed, only one of the author's patients would have been diagnosed as having spasmus nutans. From the contents of this presentation, we should learn the specific lesson that an acquired nystagmus presenting in infancy, especially if it looks like spasmus nutans, may be the first sign ofa chiasmal glioma. Moreover, whenever a "benign" syndrome such as spasmus nutans presents without some of its typical components or with associated abnormal findings (such as the optic atrophy or diencephalic syndrome seen here), then it is incumbent upon us to thoroughly evaluate the patient for the possibility of a more threatening lesion. References 1. Gresty MA, Ell JJ. Spasmus nutans or congenital nystagmus? Classification according to objective criteria (Correspondence). Sr J Ophthalmol1981; 65:510-1. 2. Gresty M, Leech J, Saunders M, Eggars H. A study of head and eye movement in spasmus nutans. Sr J Ophthalmol 1976; 60:652- 4.
435