Epilepsia Partialis
Continua Associated
With Widespread
Gliomatosis Cerebri

epilepsia partialis continua in children to facilitate a
rapid diagnosis and initiation of prompt treatment of
this rare disorder that may respond to a concurrent
effective combination of cranial radiation, chemotherapy, and antiepileptic medications. © 2002 by
Elsevier Science Inc. All rights reserved.
Shahar E, Kramer U, Nass D, Savitzki D. Epilepsia
partialis continua associated with widespread gliomatosis
cerebri. Pediatr Neurol 2002;27:392-396.

Eli Shahar, MD*, Uri Kramer, MD†,
Dvora Nass, MD‡, and David Savitzki, MD*
Introduction
We report an uncommon association of intractable
epilepsia partialis continua that was the main presentation of widespread gliomatosis cerebri in two females. Both children had a preceding prolonged secondary generalized seizure 2-4 months before the
evolution of epilepsia partialis continua, including recurrent clusters of left-sided myoclonic twitching and
sensory impairment. During these events, the children
remained fully alert. These seizures were corroborated
by prolonged focal epileptic spike/wave discharges
evident on the electroencephalograms. Cerebral magnetic resonance imaging in the first patient demonstrated a wide area of increasing signals over the right
frontocentral regions, along with diffuse cortical-subcortical infiltration impinging on the left hemisphere.
In the second patient a cortical lesion was suspected.
Evaluation for Rasmussen’s encephalitis, focal cortical
dysplasia, or a gliomatous process was conducted; the
patients underwent a stereotactic brain biopsy in
which the histologic findings were compatible with
gliomatosis cerebri with diffuse widespread infiltration
of glioma cells with no constitution of a circumscribed
tumor mass. The first patient was treated with cranial
radiation, chemotherapy, steroids, and combined antiepileptic therapy. The focal seizures gradually but
markedly decreased in frequency, and sensory impairment abated within 18 months after establishment of
the diagnosis and ensuing therapy. Cognition remains
intact. The second female died 2 years after presentation despite massive chemotherapy and antiepileptic
medications. Although rare, gliomatosis cerebri should
be taken into account in the differential diagnosis of

Epilepsia partialis continua is defined as ongoing relentless clonic muscle twitching, sometimes in rapid succession, that is mainly confined to one side of the body and
can last for weeks or months, associated with progressive
pyramidal weakness and sensory impairment, although
there is no alteration of consciousness, commonly associated with focal epileptic discharges [1-3].
Epilepsia partialis continua in adults has been associated with various underlying etiologies, including infections, cerebrovascular events, and tumors [3]. Epilepsia
partialis continua in children has most commonly been
associated with Rasmussen’s encephalitis [2,4-5], which is
a progressive autoimmune unilateral cortical destructive
process. Rasmussen encephalitis was the most common
underlying etiology of epilepsia partialis continua in children under 16 years of age in a survey of 32 patients
reported by Cockerel et al. [2]. Epilepsia partialis continua
in children was also associated with congenital structural
abnormalities of the cortex secondary to migrational disorders [6-10] however, to a lesser extent, compared with
Rasmussen’s encephalitis. These abnormalities included
focal cortical dysplasia [6-8] and hemimegalencephaly
[9-10]. Epilepsia partialis continua in children was also
rarely associated with various respiratory chain mitochondrial disorders, including the MELAS syndrome in two
young sisters [11], Leigh syndrome and partial deficiency
of cytochrome C oxydase [12], NADH-coenzyme Q reductase deficiency [13], and, in a 16-year-old male, it was
associated with a homoplastic mitochondrial tRNA
(Ser(UCN) mutation [14].
In this report, we present a unique association of
epilepsia partialis continua in two females, which was the
main clinical manifestation of gliomatosis cerebri, namely,

From the *Child Neurology Unit and Epilepsy Service; Meyer
Children Hospital; Rambam Medical Center; Haifa; the †Pediatric
Neurology Unit; Tel-Aviv Souraski Medical Center; Tel Aviv; and the
‡
Department of Pathology; Sheba Medical Center; Tel Aviv, Israel.

Communications should be addressed to:
Dr. Shahar; Child Neurology Unit & Epilepsy Service; Meyer
Children Hospital; Rambam Medical Center; Haifa 31096, Israel.
Received January 16, 2002; accepted May 13, 2002.

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Figure 1. Surface electroencephalogram using a transverse bipolar montage
demonstrates a prolonged epileptic discharge over the right frontocentral regions consisting of paroxysmal fast sharp
waves, corroborated with left-sided
twitching but preserved alertness. This
image reveals an underlying moderate
disturbance of background activity over
the right frontocentral regions.

diffuse infiltration of the normal nervous tissue with glial
cells with no concrete formation of a tumor mass [15-18].
Although focal seizures may be the presenting symptoms
in gliomatosis cerebri [18], the evolution of epilepsia
partialis continua as the main clinical perturbation of
gliomatosis cerebri is extremely rare.
Case Reports
Patient 1
A 5-year-old previously healthy female presented to a local hospital 10
months before admission to our service with an apparently secondary
generalized clonic seizure. The initial electroencephalogram reportedly
demonstrated focal epileptic activity over the right hemisphere. She was
begun on phenytoin and switched to carbamazepine after 2 months. She
remained asymptomatic for a period of 4 months after which she began
having recurrent left-sided twitching movements of the face, arm, and leg
that lasted for seconds, accompanied by a feeling of numbness over the
left upper limb but not associated with any alteration of consciousness.
Computed tomography of the brain at that point was unremarkable.
Magnetic resonance imaging, on the other hand, demonstrated increased
T2-weighted signals over the right frontocentral regions. During the next

6 months her focal motor left-sided seizures had markedly increased in
frequency to become virtually continuous, along with progressive sensory impairment, mainly of the left upper limb, despite treatment with
massive combined antiepileptic therapy, including oral carbamazepine,
valproic acid, lamotrigine, and topiramate.
The patient was admitted for evaluation at our institution 6 months
after the initiation of her left-sided focal motor seizures, which remarkably increased in frequency; yet she remained fully alert and coherent.
Motor-wise a mild-to-moderate left-sided pyramidal weakness was
detected along with brisk tendon reflexes and abnormal Babinski and
Hoffmann responses, accompanied by mild sensory impairment, namely,
tingling and numbness. She had as many as 80-100 clusters of left-sided
twitching, which only partially responded to intravenous therapy of
phenytoin and midazolam. Repeat electroencephalogram records (Fig 1)
demonstrated prolonged and recurrent spike/slow wave epileptic discharges over the right frontocentral regions along with disturbance of
background activity, corroborated by the left-sided focal motor seizures
verified with video electroencephalogram. Such a combination was
compatible with the diagnosis of epilepsia partialis continua. HMPAO
single-photon emission computed tomography cerebral scanning demonstrated marked hyperperfusion over the right frontocentral areas, suggestive of prolonged ictal activity. Ophthalmologic examination demonstrated a swollen right optic disc. Magnetic resonance imaging of the
brain (Fig 2) demonstrated a large widespread subcortical-cortical

Shahar et al: Epilepsia Partialis Continua in Gliomatosis Cerebri 393

The differential diagnoses included Rasmussen’s encephalitis, cortical
dysplasia, or a gliomatous process. A stereotactic cortical biopsy was
therefore performed, and the histologic findings were diagnostic of
gliomatosis cerebri (Fig 3). This finding demonstrated abundant infiltration of glial cells with irregular hyperchromatic nuclei and minimal
cytoplasm, without mitoses or vascular hyperplasia or tissue necrosis.
Perineural satellitosis, which is a hallmark of gliomatosis cerebri, was
evident and included engulfing of neurons by those glial cells to form a
satellite configuration (Fig 3). The overall anatomic structure was not
distorted, and there was no outlining of a tumoral mass. Immunohistochemical staining with the Ki-67 marker for cell proliferation was
negative. After the ominous diagnosis of gliomatosis cerebri, the patient
was treated with cranial radiation, repeat courses of massive combined
chemotherapy, high-dose corticosteroids, and combined antiepileptic
therapy, including phenytoin, phenobarbital, lamotrigine, and gabapentin. The focal motor clusters gradually decreased in frequency after 5
months of treatment, although she still has intermittent infrequent
left-sided twitching with no motor, sensory, or cognitive impairment
within a follow-up period of 18 months since the establishment of the
histologic diagnosis and initiation of therapy.

Patient 2

Figure 2. Magnetic resonance imaging of the brain using T2-weighted
images demonstrates a large widespread cortical-subcortical gadolinium-enhancing an ill-defined area encountering the frontocentral areas of
the right hemisphere with diffuse swelling, displacing the right midline
structures and obstructing the lumen of the right lateral ventricle.

gadolinium-enhancing area encountering the anterior two thirds of the
right hemisphere, spreading into the interhemispheral region with diffuse
swelling and displacing the right midbrain structures to the left.
Given the progressive and relentless nature of the epilepsia partialis
continua, the widespread hemispheral abnormalities depicted on magnetic resonance imaging, and the swelling of the right optic disc, a rapidly
expanding destructive cortical mass was suspected.

A 10-year-old previously healthy female presented with a prolonged
left focal motor seizures that rapidly became generalized and lasted for 2
hours overall. Electroencephalography studies demonstrated epileptiform
activity over the right centrotemporal regions, and she was begun on
carbamazepine. After 2 months she began having recurrent sensory
seizures consisting of a tingling sensation, which began over her left
upper limb and spread to the rest of her left side, which were followed by
recurrent focal motor seizures. During those events she experienced some
decrease of alertness with feeble speech; however, she never lost
consciousness and remained aware of her sensory impairment and
twitching. Concomitantly she developed a progressive left-sided weakness. Cerebral computed tomography demonstrated a calcified lowdensity lesion in the right centrotemporal regions. Magnetic resonance
imaging demonstrated a cystic mass at the right centrotempotal areas
spreading posteriorly, nonenhancing with gadolinium. The differential
diagnoses included encephalitis, inflammatory cerebritis, stroke, neurocystercosis, or gliomatosis cerebri, which seemed unlikely. The histology
of a stereotactic biopsy of this mass was diagnostic of gliomatosis
cerebri. Despite massive chemotherapy and antiepileptic medications, the
patient died 2 years after the initial presentation.

Figure 3. Hematoxylin and eosin staining of a stereotactic cortical biopsy is diagnostic of gliomatosis
cerebri. Abundant infiltration of astrocytic cells with
irregular hyperchromatic nuclei and minimal cytoplasm are illustrated, without mitoses or vascular
hyperplasia or tissue necrosis. Notice a striking satellitosis (arrows) revealing three neurons engulfed by
glial cells forming a satellite configuration. Overall
the anatomic structure was not distorted with no
outlining of a tumor mass.

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Discussion
New-onset epilepsia partialis continua in a previously
healthy child implies an ominous progressive neurologic
disorder and requires prompt diagnosis and treatment
because of the possibility of developing an infiltrative
cortical lesion. Regardless of the underlying etiology of
epilepsia partialis continua, a lack of response to antiepileptic medications using high doses in various combinations, as occurred in both patients presented in this report,
usually constitutes an alarming prognostic sign, necessitating early intervention. When conducting a search of the
literature, we could not find a collective series of epilepsia
partialis continua in the pediatric age group but found a
small number of reports depicting a variety of underlying
diagnoses, mainly including Rasmussen’s encephalitis
[4,5], congenital neuronal migration disorders [6-10], or
rare metabolic or enzymatic disorders [11-14]. Rasmussen’s encephalitis has been most commonly associated
with intractable and relentless epilepsia partialis continua
in the pediatric age group [2,4,5], consisting of progressive
cortical destruction mainly confined to one hemisphere.
After histologic diagnosis, of which the hallmark is
perivascular lymphocytic cuffing, early surgical intervention may be required to halt the progressive cortical
destruction and suppress the ongoing epilepsia partialis
continua. Relatively fewer reports describe the possible
association of neuronal migration disorders in infants and
children developing epilepsia partialis continua [6-10].
The radiologic abnormalities demonstrated by magnetic
resonance imaging may be similar in either Rasmussen’s
encephalitis or cortical dysplasia. However, the structural
abnormalities found in Rasmussen’s encephalitis are commonly unilateral and circumscribed compared with multifocal and sometimes bihemispheral parenchymal distortion and ventricular abnormalities observed in disorders of
neuronal migration.
A brain biopsy is therefore necessary to delineate the
ultimate diagnosis, either demonstrating an inflammatory
response with perivascular lymphocytic cuffing in Rasmussen’s encephalitis [4,5] or distorted cortical architecture in congenital structural anomalies of the cortex [6-10].
Fusco et al. [6] report that in a series of 50 children with
neuronal migration disorders, two children with unilateral
migrational abnormalities had developed epilepsia partialis continua, which was subtle and almost overlooked. The
same authors [8] also reported on a child with hemimeganencephaly who developed an opercular syndrome associated with persistent focal spikes, similar to that reported
by Ishii et al. [9]. Debiens et al. [10] reported on a child
with occult cortical dysplasia who developed epilepsia
partialis continua. In his review, Andermann [19] noted
that a high rate of patients with either Rasmussen’s
syndrome or neuronal migration disorders may develop
epilepsia partialis continua or other epileptic discharges
arising from the precentral gyrus. In addition, a few rare
metabolic and enzymatic disorders in children were also

associated with epilepsia partialis continua [11-14]. However, children affected by such disorders usually suffer
from associated cognitive, verbal, and motor handicaps,
even before the emergence of the epilepsia partialis
continua and, therefore, could be fairly easily differentiated from those with structural anomalies, such Rasmussen’s encephalitis, inducing epilepsia partialis continua.
Gliomatosis cerebri is a rare and unique neoplastic
disorder characterized by diffuse widespread proliferation
of neoplastic glial cells within the cortex, with no constitution of a discrete tumoral mass, mostly involving the
gray matter but may also spread to the white matter
[15-18]. Histologic evaluation reveals neoplastic astrocytes with varying degrees of differentiation, of which
many cells display elongated twisted nuclei reminiscent of
microglia, stained intensely for glial fibrillary acidic protein, with relative preservation of the underlying cytoarchitecture [16].
Concerning the underlying pathogenesis of gliomatosis
cerebri that to date has not been fully clarified, Artigas et
al. [16] postulated on the basis of the two-stage theory of
carcinogenesis that gliomatosis cerebri may be the result
of the propagation of primitive glial elements that have not
undergone the process of tumor conversion, after analyzing the histology of 58 patients with gliomatosis cerebri.
Gliomatosis cerebri rarely has been reported in the pediatric age group, including in neonates, and mainly presents
with seizures [18,20]. Other reports include gliomatosis
cerebri in a 7-year-old child masquerading as pontine
glioma with involvement of the entire neuroaxis [21],
gliomatosis cerebri in a 10-year-old female masquerading
as diffuse encephalomyelitis and a spinal cord tumor [22],
gliomatosis cerebri in a 14-year-female with progressive
dementia [23], and gliomatosis cerebri in a 16-year-old
adolescent presenting with unilateral third nerve palsy
[24].
The clinical presentations associated with gliomatosis
cerebri are variable, depending on the extent and the
region affected by the neoplastic glial cells, and may also
be age related. Adults, more commonly the elderly, may
present with progressive dementia, affective and mental
changes, and corticospinal tract perturbations [15-17],
whereas children may more readily present with seizures
and cranial neuropathies [18]. Couch and Weiss [15]
reviewed 36 cases with gliomatosis cerebri, which mainly
included adults, and report that the most common presentation included alterations in mental status and personality
followed by pyramidal hemiparesis, cerebellar impairment, papilledema, headaches, seizures, and brainstem
signs, in decreasing order. The most comprehensive review on gliomatosis cerebri was published by Jennings et
al. [18] who reported on 160 cases of gliomatosis cerebri
retrieved from the literature. The most common abnormalities in 139 patients at all ages included corticospinal tract
deficits in 58%, dementia or mental retardation in 44%,
headaches in 39%, seizures (mainly focal) in 38%, cranial

Shahar et al: Epilepsia Partialis Continua in Gliomatosis Cerebri 395

neuropathies in 37%, benign increased intracranial pressure in 34%, and spinocerebellar deficits in 33%. The
cerebrum, including the centrum semiovale, was infiltrated in 76% of patients with gliomatosis cerebri, as was
the case in the first child presented here with massive
infiltration. Jennings et al. [18] also reported on three
children in whom a diagnosis of gliomatosis cerebri was
established at the ages of 6 days, 8 months, and 6 years,
respectively. The neonate presented with right focal seizures that rapidly became generalized, having had repeat
nonresponsive episodes of status epilepticus leading to his
death. The 8-month-old infant initially had generalized
extensor spasms and recurrent myoclonic jerks of upper
extremities, representing infantile spasms, that effectively
responded to oral steroids. After control of these seizures
was established, he developed a right-sided epilepsia
partialis continua. The third child also had generalized
myoclonic seizures associated with gliomatosis cerebri.
All patients had focal electroencephalogram discharges
corroborating with unilateral parenchymal changes, implying secondary generalization of the focal epileptic discharges from the regions of the gliomatous spread, similar
to the patients presented in this report.
The patients presented herein developed epilepsia partialis continua, intractable to antiepileptic medications,
lasting for months before the clinical and electroencephalogram diagnosis of epilepsia partialis continua was established, subsequently undergoing a cortical biopsy in an
attempt to identify the underlying etiology. The differential diagnoses in a previously healthy child who develops
epilepsia partialis continua, corroborated by hypersignal
lesions on magnetic resonance imaging suspecting a structural cortical lesion, includes Rasmussen’s encephalitis,
disorders of neuronal migration, and, rarely, a gliomatous
process such as gliomatosis cerebri, as occurred in both
patients presented in this study. Epilepsia partialis continua, which was the single clinical presentation of gliomatosis cerebri in both patients, with no other neurologic
abnormalities is unusual and intriguing considering the
other various and mixed presentations of gliomatosis
cerebri. The outcome of children with diffuse widespread
gliomatosis cerebri is currently unpredictable because of
the possible beneficial effects of the current potent chemotherapeutic drug combinations after cranial radiotherapy and the effectiveness of antiepileptic medications, as
occurred in the first female presented herein. Therefore,
gliomatosis cerebri should be taken into account in any
previously healthy child presenting with new-onset epilepsia partialis continua corroborating with unilateral spreading lesions visible on magnetic resonance imaging, and
hence the importance of readily performing a cortical
biopsy to rapidly establish the accurate diagnosis and
enable prompt treatment.

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