Short Reports

tive reaction for Synaptophysin and Chromogranin. The picture was

consistent with desmoplastic infantile ganglioglioma.

Discussion
Desmoplastic supratentorial neuroepithelial tumors of infancy form a rare but distinctive group of tumors occurring in
children less than 2 years of age. Vanden Berg et al1 (1987),
named these tumors as desmoplastic cerebral astrocytoma of
infancy and desmoplastic infantile ganglioglioma (DIG), on
the basis of immunohistochemistry and electron microscopy.
Both these groups of tumors occur in children less than 2
years of age. They have identical clinical and radiological features and both have favorable outcome following successful
excision. Subsequently, these groups of tumors have been included as a distinctive group, in the revised World Health
Organization (WHO) classification of brain tumors (Kleihues
et al21993).
Less than 50 cases of desmoplastic infantile ganglioglioma
(DIG) have been reported in the literature. Several authors
have reported single case reports and small series of cases of
DIG.3,4 The youngest patient has been 4 months of age. All
these children presented with macrocephaly, seizures, psychomotor delay, either in isolation or in combination. All these
patients have similar Computerized Tomographic scan (CT)
and Magnetic Resonance Imaging (MRI) characteristics (Martin et al 1991, Tenreiro-Picon et al5,6 1995). The tumors commonly occur in frontal or parietal lobes, with a solid component closely attached to the dura, which intensely enhances
with contrast, surrounded by a parenchymal cystic component and mass effect. Most of these tumors are amenable to

surgical excision because of their surface location and distinct

firmness with clear demarcation from the surrounding normal brain. No adjuvant therapy is recommended after total
excision, despite the fact that the lesion has a low malignant
potential. Long-term prognosis after total surgical excision
has been excellent in all the reported series.
Histologically, these tumors have intense desmoplasia, with
neoplastic astrocytes with occasional neuronal elements.
Desmoplastic cerebral astrocytoma of infancy and DIG are
difficult to differentiate under light microscopy. Immunohistochemistry plays a very important role in the diagnosis of
DIG. In DIG, the tumor shows intense positivity for Glial
Fibrillary Acidic Protein (GFAP) which is a glial marker, with
areas positive for synaptophysin or neurofilament
immunostain, which are neuronal markers. In desmoplastic1,4,7
cerebral astrocytoma, there is positivity for GFAP only.

References
1.

2.
3.
4.

5.
6.
7.

Vanden Berg SR, May EE, Rubeinstein LJ, et al. Desmoplastic supratentorial
neuroepithelial tumors of infancy with divergent differentiation potential
(desmoplastic infantile gangliogliomas). J Neurosurg 1987;66:58-71.
Kleihues P, Burger PC, Scheithauer BW. The new WHO classification of brain
tumors. Brain Pathol 1993;3:255-68.
Duffner PK, Burger PC, Cohen ME, et al. Desmoplastic infantile
gangliogliomas: An approach to therapy. Neurosurg 1994;34:583-9.
Sperner J, Gottschalk J, Neumann K, et al. Clinical, radiological and histological findings in desmoplastic infantile ganglioglioma. Childs Nerv Syst
1994;10:458-63.
Martin DS, Levy B, Awwad EE, et al. Desmoplastic infantile ganglioglioma:
CT and MR features. Am J Neuroradiol. 1991;12:1195-7.
Tenreiro-Picon OR, Kamath SV, Knorr JR, et al. Desmoplastic infantile
ganglioglioma: CT and MRI features. Pediatr Radiol 1995;25:540-3.
VandenBerg SR. Desmoplastic infantile ganglioglioma and desmoplastic cerebral astrocytoma of infancy. Brain Pathol 1993;3:275-81.

Accepted on 11.11.2003.

Total external ophthalmoplegia induced by phenytoin: A case

report and review of literature
Vinod Puri, Neera Chaudhry
Department of Neurology, G. B. Pant Hospital, New Delhi - 110002, India.

A 28-year-old male developed total external ophthalmoplegia following oral administration of phenytoin. The case is
reported and its significance is discussed.
Key Words: External ophtalmoplegia, Phenytoin induced
ophtalmoplegia, phenytoin toxicity.

Introduction
There have been innumerable reports concerning phenytoin
toxicity, but few have mentioned its effects on eye movements
other than nystagmus.1 Ophthalmoplegia has been reported
with administration of large doses of Phenytoin,2,3 Phenobar-

Vinod Puri
16, Type 5, MAMC Campus, New Delhi - 110002, India. E-mail: vpuri@bol.net.in

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bitone, Primodone, Carbamazepine and Amitriptyline. Spector

et al2 reported that phenytoin could induce total external ophthalmoplegia irrespective of oral or intravenous administration. Incomplete4 as well as complete ophthalmoplegia5 has
been reported with phenytoin even within therapeutic range.
We present a patient with phenytoin intoxication who developed disturbances in the ocular movements.

Case Report
A 28-year-old mentally retarded male, with IQ-55, had generalized tonic-clonic epilepsy for two years. He was placed on
carbamazepine (Tegretol) 800mg per day. However, due to financial
reasons, he was irregular with his treatment. Subsequently, he was
placed on Diphenyl hydantoin (300mg per day). After about two
weeks of the change in the drug treatment he reported inability to
move his eyes. He denied excessive ingestion of the drug. The pupils
were 5mm in diameter, round, equal and reacting well to light. The
gaze was fixed directly forward. The patient did not move his eyes on
command and could not follow the light. The eyes could not be moved
by head turning or neck bending or by irrigation of the ears with ice
water. Fundi were normal. The rest of the neurological examination
was normal. The cerebrospinal fluid examination was normal. The
CT of the head was normal. The phenytoin drug level was 22 microgm
per ml. The phenytoin was withdrawn and he was given loading dose
of phenobarbitone, followed by its maintenance dose. On the fifth
day, he could move his eyes about 100 in horizontal direction (laterally and medially) but was unable to move them in the vertical direction. On the seventh day, the horizontal movements had improved
and he could move the eyes slightly downward but not upward. Irrigation of the left ear with ice cold water produced no movements of
the eyes but irrigation of right ear produced occasional nystagmus
with fast component to the left. On the eleventh day his eye movements were normal. He was seizure-free on 120 mgm of phenobarbitone per day.

rigation may occur even when the blood phenytoin level is

within the accepted therapeutic range.
GABA mediates the inhibition of oculomotor neurons produced by the vestibular system. Phenytoin increases the postsynaptic potentials produced by GABA in the cerebral cortex7
and the spinal cord. Spector et al2 attributed the unresponsive cold caloric irrigation with phenytoin to an increased effectiveness of GABA-induced inhibition at the synapses of the
vestibulo-oculomotor system. The lag in the recovery of the
oculovestibular response in the present case could be explained
with the above said hypothesis.
The cerebellum has an inhibitory role over the vestibular
ocular reflex through Purkinje cells. Phenytoin increases the
rate of Purkinje cell discharge.8 Whether this phenytoin-augmented Purkinje cell firing would act in a manner analogous
to electric stimulation of the cerebellar cortex and result in
the depression of transmission through the vestibular nucleus
and affect the normal function of the vestibulo-ocular apparatus is unclear. The majority of the reported cases of phenytoin-induced ophthalmoplegia recovered completely over a
variable period with normalization of the phenytoin level.
The present case is unique; in spite of the drug toxicity the
patient was alert and had bilateral external ophthalmoplegia
with loss of oculocephalic and oculovestibular reflexes. The
recognition of this entity is important to avoid unnecessary
investigations in a patient on phenytoin.

References
1.

2.
3.

Discussion
Phenytoin is a vestibular depressant.6 Spector et al2 observed
that the return of vestibulo-ocular response in their patients
with phenytoin intoxication lagged behind the return of consciousness and other reflex activities and attributed it to its
depressant effect on the vestibulo-oculomotor system which
may be out of proportion to its actions on other levels of the
neuraxis. The oculomotor unresponsiveness to cold caloric ir-

4.
5.
6.
7.
8.

Remler BF, Leigh RJ, Osorio I, Tomsak RL. The characteristics and mechanisms of visual disturbance associated with anticonvulsant therapy. Neurology
1990;40:791-6.
Spector RH, Davidoff RA, Schwartzman RJ. Phenytoin-induced ophthalmoplegia. Neurology 1976;26:1031-4.
Fredericks CA, Giannotta SL, Sadun AA. Dilantin-induced long-term bilateral
total external ophthalmoplegia. Clin Neuro ophthalmol 1986;6:22-6.
Manlapaz JS: Abducens nerve palsy in Dilatin intoxication. J Pediatr
1959;55:73-4.
Sandyk R. Total external ophthalmoplegia induced by phenytoin. A case report. S Afr Med J 1984;28;65:141-2.
Posner JB, Plum F: Diagnostic significance of vestibulo-ocular responses. Neurol
Neurosurg Psychiatry 1975;38:727-8.
Davidoff RA: Dipenylhydantoin increases spinal presynaptic inhibition. Trans
Am Neurol Assoc 1972;97:193-5.
Halpern LM, Julien RM: Augmentation of cerebellar Purkinje cell discharge
rate after diphenylhydantoin. Epilepsia 1972,13:377-85.

Accepted on 12.06.2003.

Calvarial malignant fibrous histiocytoma

R. Chhabra, S. K. Gupta, K. S. Manjunath Prasad, D. Gupta*, R. K. Vasishta*, R. K. Sharma**,
V. K. Khosla
Departments of Neurosurgery, *Pathology and **Plastic Surgery , PGIMER, Chandigarh, India.

S. K. Gupta
Additional Professor, Department of Neurosurgery, PGIMER, Chandigarh - 160012, India. E-mail: sktulika@yahoo.com

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