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case records of the massachusetts general hospital

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Case 34-2014: A 7-Year-Old Boy with Focal

Seizures and Progressive Weakness
Ronald L. Thibert, D.O., M.S.P.H., Ann-Christine Duhaime, M.D.,
Paul A. Caruso, M.D., and Anat Stemmer-Rachamimov, M.D.

Pr e sen tat ion of C a se

Dr. Michael Ho (Neurology): A 7-year-old boy was evaluated in an outpatient clinic at From the Departments of Neurology
this hospital because of focal seizures and progressive right-sided weakness. (R.L.T.), Neurosurgery (A.-C.D.), Radiol
ogy (P.A.C.), and Pathology (A.S.-R.),
The patient had been well until 18 months earlier, when intermittent shaking Massachusetts General Hospital, and the
of his right hand developed, which quickly progressed to involve the entire right Departments of Neurology (R.L.T.), Neuro
arm. Evaluation at another hospital included electroencephalography (EEG) that surgery (A.-C.D.), Radiology (P.A.C.), and
Pathology (A.S.-R.), Harvard Medical
revealed frequent left-sided discharges, magnetic resonance imaging (MRI) of the School both in Boston.
head that revealed no clear atrophy but a lesion in the left motor strip, and a lum-
N Engl J Med 2014;371:1737-46.
bar puncture with normal results on cerebrospinal fluid analysis. A diagnosis of DOI: 10.1056/NEJMcpc1305993
focal motor seizures was made; levetiracetam and glucocorticoids were adminis- Copyright 2014 Massachusetts Medical Society.

tered. Approximately 2 months after the onset of symptoms, twitching of the arm
and hand became nearly constant and was accompanied by facial twitching; a
clinical diagnosis of epilepsia partialis continua was made. Intravenous immune
globulin was administered, and the twitching in his face and arm almost com-
pletely resolved. Approximately 3 months later, however, the symptoms recurred.
During the year before this evaluation, the right arm and the right side of the
face began to twitch nearly continuously, with more intense focal clonic activity
occurring 2 to 20 times per day; there was associated progressive weakness of the
muscles of the right arm (more severe distally than proximally) and the right side
of the face, increasing spasticity in the fingers and wrist, and subtle weakness of
the right leg. There was no history of loss of consciousness, apnea, cyanosis, or
seizure activity involving the left side. MRI studies of the head that were performed
between 9 months and 3 months before this evaluation reportedly revealed a T2-
weighted hyperintense lesion in the left motor strip involving the adjacent white
matter and, in more recent studies, the parietal region, with no clear evidence of
atrophy. A brain biopsy was recommended. The family sought a second opinion at
this hospital.
The patient was born at 36 weeks of gestation after the onset of preterm labor
and had normal or advanced developmental milestones (including reading at 3 years
of age). He had reactive airway disease and had undergone tonsillectomy, adenoid-
ectomy, and urologic surgery. Medications included levetiracetam (800 mg twice

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 The n e w e ng l a n d j o u r na l
daily), clonazepam (0.5 mg in the morning and
1 mg in the evening), oxcarbazepine (360 mg in
the morning and 420 mg in the evening), val-
proic acid (375 mg twice daily), lipoic acid, vita-
min B6, and coenzyme Q10. Immunizations were
current. He had no known drug allergies. He
consumed a ketogenic diet (a high-fat, low-carbo-
hydrate diet), which helped to control his sei-
zures, and he participated in occupational and
physical therapy. He lived with his parents and
older sibling, was in second grade, and did well
academically. His mother and sibling had atten-
tion deficithyperactivity disorder, a paternal aunt
had bipolar disorder, and other paternal relatives
had depression.
On examination, the patient was awake, alert,
and pleasant. His speech was clear and fluent,
with mild dysarthria. He seemed to be intelligent,
with good social skills. The pupils and extra-
ocular movements were normal. There was weak-
ness on the right side of the face, the palate was
elevated symmetrically, and the tongue protruded
along the midline. There was nearly continuous
twitching of the right lower facial muscles.
Muscle bulk, tone, and strength were normal in
the left arm and leg. In the right arm, strength
was 4/5 proximally, with little movement of the
fingers or wrist and distal-muscle spasticity.
Strength in the right leg was 4+/5, with slightly
increased reflexes. The gait was mildly hemipa-
retic. A brain biopsy was recommended, and the
family resumed care at the other hospital.
During the next 6 months, twitching was
constant in the right side of the face and nearly
continuous in the right arm. The focal seizures
in the right side of the face and right arm and
leg (which frequently caused the patient to fall)
occurred up to 20 times daily when he was tired
or sick or had not adhered to his diet. Weakness
of the right leg and arm increased, and his gait
became more hemiparetic, despite continued
medical therapy with levetiracetam, clonazepam,
oxcarbazepine, and valproic acid and general
adherence to the ketogenic diet.
Six months after the initial evaluation at this
hospital, the patient returned to this hospital for
care. Magnetoencephalography (MEG) revealed
seizure activity in the left frontal lobe, with dis-
charges predominantly in the posterior left fron-
tal cortex, along the frontal operculum of the
motor cortex (precentral gyrus) and the area as-
sociated with control of the hand, and abnormal
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of m e dic i n e
somatosensory-evoked magnetic fields in the
left hemisphere, findings suggestive of cortical
dysfunction. During the MEG recording, there
was continuous right facial twitching and some
evidence that the right hemisphere was domi-
nant for language.
Three months later, the patient was admitted
to this hospital. A 24-hour EEG showed that the
focus of his continuous right facial twitching was
in the left frontal area, with a broad electrical
field involving the entire left hemisphere. EEG
also recorded six generalized tonicclonic sei-
zures characterized by spike-and-wave discharges
(1 to 2 Hz); the site of maximal amplitude was
the midline central region, and the duration was
approximately 15 to 40 seconds.
The next day, a diagnostic procedure was per-
formed.
Differ en t i a l Di agnosis
Dr. Paul A. Caruso: The neuroimaging studies re-
veal the following two principal pathological fea-
tures: progressive atrophy in the left cerebral
hemisphere, and a focal lesion that raises the
possibility of focal cortical dysplasia or inflam-
mation. The progressive atrophy in the left cere-
bral hemisphere is seen on the series of axial
T2-weighted images obtained when the patient
was between 6 years of age and 8 years of age
(Fig. 1). During this period, the left inferior, mid-
dle, and superior frontal sulci and left parieto-
occipital sulci enlarge progressively and the un-
derlying cortex thins segmentally, findings that
reflect progressive cortical atrophy and loss of
white-matter volume.
The focal lesion with high signal intensity
that is seen on T2-weighted images (Fig. 2A)
involves the left precentral and postcentral gyral
cortex (including the motor strip) and subcorti-
cal white matter, and trails radially through the
deep white matter toward the left lateral ventri-
cle; these features are suggestive of focal cortical
dysplasia. Magnetic resonance spectroscopy that
was performed over the lesion (Fig. 2B) reveals
a decrease in the ratio of N-acetylaspartate to
creatine but no increase in the ratio of choline
to creatine, features that may also be associated
with focal cortical dysplasia.
MEG was performed to evaluate the distribu-
tion of epileptogenic foci in the left cerebral
hemisphere. MEG is a neuroimaging technique
 case records of the massachuset ts gener al hospital

A B C

D E F

Figure 1. MRI Scans of the Head at 6, 7, and 8 Years of Age.

A series of axial T2 -weighted images were taken from MRI studies of the head that were performed when the patient
was 6 years of age (Panels A and B), 7 years of age (Panels C and D), and 8 years of age (Panels E and F). Progressive
enlargement of the cerebral sulci and contraction of the gyri in the left cerebral hemisphere are shown at the level of
the cerebral peduncles (Panels A, C, and E) and at the level of the lateral ventricles (Panels B, D, and F); these pro-
gressive findings are consistent with atrophy in the left cerebral hemisphere.

that uses biomagnetism to produce an image of
the brain. As a result of the behavior described
by Maxwells equations, electric currents induce
orthogonally directed magnetic fields. MEG uses
the magnetic fields induced by cerebral neuronal
electric currents to determine the location of
electric (neuronal) activity in the brain. The elec-
tric activity is represented as equivalent dipoles
(see blue dots and dashes in Fig. 1 in the
Supplementary Appendix, available with the full
text of this article at NEJM.org). In this case,
MEG shows that the magnetic dipoles overlap
but cluster mostly lateral and inferior to the
focal lesion in the atrophied left cerebral hemi-
sphere.
Dr. Ronald L. Thibert: The differential diagnosis
of refractory epilepsy is very broad, so this dis-
cussion will focus on the differential diagnosis
of this patients specific seizure type, which is
rare in children. His clinical seizure activity is
most consistent with epilepsia partialis continua,
which is defined as almost continuous regular
or irregular muscular clonic twitching affecting
a limited part of the body.1 Consciousness is
typically preserved, and the twitching most
commonly involves the face, arms, or both.
According to the definition of epilepsia partialis
continua, the twitching must last at least 1 hour
(but may last hours or years) and the twitches
must occur at least once every 10 seconds, typi-
cally in isolation or in clusters of 1 to 2 Hz.
The differential diagnosis for epilepsia parti-

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 The n e w e ng l a n d j o u r na l of m e dic i n e

A Table 1. Differential Diagnosis of Epilepsia Partialis

Continua.*

Nonprogressive causes
Vascular causes (stroke, cerebral venous sinus throm-
bosis)
Metabolic causes (hyperosmolar hyperglycemic non-
ketotic syndrome, hyponatremia)
Neoplasm (central nervous system neoplasm or
hematologic neoplasm)
Infectious or immunologic causes (human immuno-
deficiency virus, encephalitis)
Cortical dysplasia
Mitochondrial causes or inborn error of metabolism
Perinatal central nervous system injury
B Cryptogenic causes
Progressive cause
Rasmussens encephalitis

* Data are from Sinha and Satishchandra,2 Phabphal et al.,3

and Kravljanac et al.4

On the basis of this patients clinical presen-

Figure 2. Imaging Studies of the Head at 7 Years of Age.
A coronal fluid-attenuated inversion recovery (FLAIR)
image from MRI performed at 7 years of age (Panel A)
shows a lesion with high signal intensity (arrows) in
the precentral and postcentral gyri that involves the
cortex and subcortical white matter and trails infero-
medially toward the left lateral ventricle, features that
are suggestive of focal cortical dysplasia. Multivoxel
magnetic resonance spectroscopy performed over the
lesion at an echo time of 288 msec (Panel B) reveals a
decrease in the ratio of N-acetylaspartate to creatine
(arrows) but no increase in the ratio of choline to creatine.
alis continua is divided into nonprogressive and
progressive causes (Table 1); this patients clini-
cal presentation is most consistent with a pro-
gressive process. Much of the literature on epi-
lepsia partialis continua focuses on adults, but a
recent study involving 51 children with epilepsia
partialis continua4 showed that Rasmussens
encephalitis was the most common cause, with
other common causes including immune or in-
flammatory processes (e.g., acute and subacute
encephalitis and subacute sclerosing panenceph-
alitis), metabolic disorders (e.g., mitochondrial
disease and neuronal ceroid lipofuscinosis), cor-
tical malformations, and vascular causes.
tation and neuroimaging studies, the two most
likely causes of the epilepsia partialis continua
are Rasmussens encephalitis and cortical dys-
plasia. Rasmussens encephalitis, which was
first described in 1958 by Dr. Theodore Ras-
mussen, is a progressive neurologic disease of
unknown cause (Table 2). Patients typically
present in childhood with focal-onset seizures,
which then progress over a period of months to
refractory epilepsy with progressive hemiparesis.
Epilepsia partialis continua develops in approxi-
mately 50 to 90% of persons with Rasmussens
encephalitis, and fixed hemiparesis typically oc-
curs within 2 to 3 years after the onset of sei-
zures. Seizures are typically refractory to medi-
cation, as was the case with this patient, but
glucocorticoids and intravenous immune globu-
lin can be effective in controlling seizures.
Various other immunosuppressive medications
have been tried, but the most effective therapy
remains hemispherectomy.
This patient had normal development before
the onset of symptoms and no other symptoms
of metabolic disease or infection; therefore, the
most likely cause of epilepsia partialis continua
in this patient is Rasmussens encephalitis or
cortical dysplasia. Malformations of cortical
development are present at birth and often cause
refractory epilepsy, but they do not typically lead

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 case records of the massachuset ts gener al hospital
to progressive hemiparesis. In some cases, how-
ever, dysplasia can mimic Rasmussens encepha-
litis and can cause motor symptoms when the
motor strip is involved.
In patients with epilepsia partialis continua,
interictal activity on EEG typically consists of
focal or generalized background slowing and
focal or multifocal epileptiform discharges, in
some cases periodic lateralized epileptiform dis-
charges. Ictal activity on EEG is variable and
may consist of focal slowing, rhythmic spike-
and-wave activity, or an electrodecrement (an epi-
sode of voltage attenuation occurring at the same
time as an epileptic spasm).6
On EEG, Rasmussens encephalitis is typi-
cally manifested by slowing and attenuation in
the affected hemisphere, with multifocal dis-
charges confined to the same hemisphere. A re-
cent study comparing the EEG findings associ-
ated with Rasmussens encephalitis with the
EEG findings associated with cortical dysplasia7
showed no marked differences between the two,
but it showed that slowing in one hemisphere is
typical among persons with Rasmussens en-
cephalitis and that there is a higher prevalence
of contralateral discharges among persons with
Rasmussens encephalitis than among persons
with cortical dysplasia. Furthermore, the contra-
lateral discharges were predictive of cognitive
decline, and it was suggested that contralateral
discharges could be an indication for resective
surgery. This patient has focal slowing that is
clearly located in the left hemisphere and most
prominent in the left frontocentral region, with
some spread to the vertex and the right fronto-
central region (Fig. 2 in the Supplementary
Appendix). These findings are suggestive of
Rasmussens encephalitis but could still be con-
sistent with cortical dysplasia in the left fronto-
central region.
It is possible that this patient has both Ras
mussens encephalitis and cortical dysplasia. In
one case series involving seven patients8 and in
individual case reports,9,10 there is histologic
evidence of coexisting cortical dysplasia and
Rasmussens encephalitis, but it is still unclear
whether these cases represent two distinct pro-
cesses. Case reports and series have also docu-
mented Rasmussens encephalitis with coexist-
ing anaplastic astrocytoma, ganglioglioma, and
findings suggestive of the tuberous sclerosis
complex.11,12
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Table 2. Diagnostic Criteria for Rasmussens Encephalitis.*
Part A (all three)
Focal seizures (with or without epilepsia partialis
continua) and unilateral cortical deficits
On EEG: unilateral hemispheric slowing (with or
without epileptiform activity) and unilateral
seizure onset
On MRI: unilateral hemispheric progressive cortical
atrophy and one of the following findings
Hyperintense signal abnormality or atrophy of
ipsilateral caudate head
Gray- or white-matter hyperintensity on T2-weighted
FLAIR images
Part B (two of three)
Epilepsia partialis continua or progressive cortical
deficits
On MRI: unilateral hemispheric progressive cortical
atrophy
One of the following groups of histopathological
features:
T-celldominated encephalitis with activated
microglial cells (typically but not necessarily
forming nodules) and reactive astrogliosis
Numerous parenchymal macrophages (B cells,
plasma cells, or viral inclusion bodies rule out a
diagnosis of Rasmussens encephalitis)
* These diagnostic criteria were described in the 2005
European Consensus Statement by Bien et al.5 Diagnosis
requires that the criteria in either Part A or Part B be met.
EEG denotes electroencephalogram, and FLAIR fluid-
attenuated inversion recovery.
DR . RONA L D L . THIBER T S
DI AGNOSIS
Rasmussens encephalitis, possibly with cortical
dysplasia.
Pathol o gic a l Discussion
Dr. Anat Stemmer-Rachamimov: Pathological exami-
nation of a biopsy specimen of the left frontal
lobe reveals a single small focus of intracortical
chronic inflammation composed predominantly
of CD3+ T cells scattered in the parenchyma and
clustered around small blood vessels (Fig. 3A
and 3B). In addition, immunohistochemical
staining for CD68 and CD163 reveals focal,
marked microglial activation (Fig. 3C). These
findings are associated with reactive gliosis, fo-
cal neuronophagia, and loss of individual neu-
rons from an otherwise well-laminated cerebral
1741
 The n e w e ng l a n d j o u r na l of m e dic i n e

A B

C D

E F

Figure 3. Biopsy and Resection Specimens of the Left Frontal Lobe.

Hematoxylin and eosin staining of the biopsy specimen shows increased cellularity in the cortex due to lymphocytic
infiltrates (Panel A). Immunohistochemical staining of the biopsy specimen for CD3 reveals that most of the lym-
phocytes are CD3+ T cells (Panel B). Immunohistochemical staining of the biopsy specimen for CD68 reveals prom-
inent microglial activation (Panel C), and immunohistochemical staining of the resection specimen for CD68 reveals
microglial nodules (Panel D). Immunohistochemical staining of the resection specimen for glial fibrillary acidic pro-
tein (GFAP) highlights many intracortical reactive astrocytes (Panel E). Immunohistochemical staining for neuronal
nuclei in an area of the resection specimen that was considered suspicious for cortical dysplasia on imaging studies
shows normal cortical lamination (Panel F).

cortex. There is no evidence of cortical dysplasia Discussion of M a nagemen t

or other malformations. These findings are not
specific for Rasmussens encephalitis, but in the Dr. Ann-Christine Duhaime: Making the decision to
appropriate clinical context, they would be con- perform surgery for the treatment of intractable
sistent with the diagnosis. epilepsy requires weighing the potential risks

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 case records of the massachuset ts gener al hospital
against the potential benefits. We need to pay
specific attention to how definitively we can lo-
calize the seizure-onset zone and how reliably we
can predict the deficits that will result from re-
section of that zone. In this patient, the differen-
tial diagnosis of the seizures includes Rasmus-
sens encephalitis, focal cortical dysplasia, and a
combination of both conditions.
In patients with intractable epilepsia partialis
continua that arises from an area of focal corti-
cal dysplasia, control of seizures generally re-
quires resection of as much of that area as pos-
sible.13,14 Risks in this situation depend on the
function of that area of the brain and of the area
immediately surrounding the dysplastic tissue. If
dysplasia is located in the rolandic area (the
motor area of the cerebral cortex that is just
anterior to the central sulcus and accounts for
part of the precentral gyrus), as in this case,
contralateral weakness or paralysis is the ex-
pected outcome of complete resection of the af-
fected tissue.
In contrast, treatment of Rasmussens en-
cephalitis requires removal or disconnection of
the entire affected hemisphere. Focal resection
has not been shown to be effective in the treat-
ment of this disorder, but hemispheric proce-
dures are associated with a high rate of success
in stopping seizures and also halting progres-
sion of the disease. Over time, a number of
techniques have been developed to accomplish
this goal, ranging from complete anatomical
hemispherectomy to newer, less extensive proce-
dures that disconnect the affected hemisphere
from the opposite hemisphere and from the re-
mainder of the nervous system.15 With hemi-
spheric disconnection, the affected hemisphere
continues to have seizure activity but the dis-
charges cannot propagate and do not produce
symptoms. The less extensive procedures are
associated with less blood loss and fewer long-
term complications but with a slightly lower
likelihood of seizure control.16-18
Hemispherectomy and hemispheric disconnec-
tion can each result in varying degrees of con-
tralateral weakness, language and other cogni-
tive dysfunction, and hemianopsia, depending
on the degree to which such functions already
have been or can be subserved by the contralat-
eral hemisphere. The ultimate outcome of either
procedure depends on a number of factors, in-
cluding neurologic condition before surgery and
degree of brain plasticity. Most children who
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undergo resection of the rolandic cortex because
of congenital problems have some weakness but
preservation of most other functions. After a
patient has undergone anatomical hemispherec-
tomy or hemispheric disconnection, the long-
term outcome typically includes spastic hemiple-
gia with return of ambulation (patients can walk
but have a spastic-type limp), development of a
helper arm without fine motor manipulative
abilities (patients can use the arm to help lift
objects but cannot perform fine motor functions
with the hand), permanent hemianopsia, and
various degrees of language and cognitive func-
tion (depending on preoperative status and age
at surgery).
In this case, in order to decide whether to
perform focal resection of the region containing
the abnormality that was seen on fluid-attenuated
inversion recovery (FLAIR) MRI imaging or to
perform hemispheric disconnection, we had to
determine whether the patient was more likely
to have focal cortical dysplasia or Rasmussens
encephalitis, on the basis of the course of the
disease, EEG findings, and radiologic evaluation.
We favored a diagnosis of Rasmussens encepha-
litis, but we could not rule out focal cortical
dysplasia. In a case like this one, in which the
seizure-onset zone cannot be determined by
noninvasive means, surgical implantation of in-
tracranial electrodes for direct monitoring of the
brain parenchyma over a period of days or weeks
is the typical strategy. However, in this case, we
decided to use an approach that involved multi-
ple methods in an attempt to determine, during
a single operation, which disorder was the most
likely cause of the patients intractable epilepsy
and thus to determine which surgical procedure
to undertake.
The team worked out the following strategy.
During the operation, we would use intraopera-
tive MRI-guided stereotactic localization to ex-
pose the area of the brain that included the ab-
normality that was seen on FLAIR imaging, as
well as the adjacent regions needed for hemi-
spheric disconnection. We would perform intra-
operative electrocorticography before any resec-
tion to determine whether a focal epileptogenic
zone could be identified. We would then resect
the presumptive dysplastic region and send a
sample of the tissue for frozen-section analysis,
to see whether there were features consistent
with dysplasia or inflammation. After the focal
resection, we would perform repeat electrocorti-
1743
 The n e w e ng l a n d j o u r na l
cography; if seizure activity was absent and the
pathological findings were suggestive of dyspla-
sia, surgery would be terminated. However, if
continued epileptiform discharges were identi-
fied outside the zone of focal resection and if
the pathological findings were suggestive of an
inflammatory process, we would then proceed
with hemispheric disconnection.
We began by performing a large, vessel-sparing
resection of the rolandic region, which we iden-
tified with the use of image guidance as the
area containing the abnormality that was seen
on FLAIR imaging. A review of frozen sections by
the pathology service revealed no findings sug-
gestive of cortical dysplasia. Electrocorticography
revealed continued discharges in the frontal and
occipital cortex. For these reasons, we proceeded
as planned with hemispheric disconnection. The
procedure involved resection of the anterior tem-
poral lobe, intraventricular disconnection of the
perisylvian cortex, intraventricular section of the
corpus callosum, and section through the medial
frontal and posterior periventricular white-matter
tracts. When the patient awoke after the surgical
procedure, he had slower psychomotor function
but was immediately able to follow commands
and name objects, and he had preserved ability
to move his right arm and minimal movement
in his right leg. The epilepsia partialis continua
was absent. During the following days, tone re-
turned in the right leg, and by 2 weeks after the
procedure, he was walking with assistance and
using his right arm.
Pathol o gic a l Discussion
Dr. Stemmer-Rachamimov: The histologic features
of the resection specimen are similar to those of
the biopsy specimen but more diffuse and more
pronounced. There is a chronic inflammatory
infiltrate in the leptomeninges. The underlying
cortex is hypercellular, with scattered intrapa-
renchymal lymphocytes, cuffs of perivascular
lymphocytes, and numerous activated microglia
(highlighted by immunohistochemical staining
for CD68), some of which were tightly clustered
and formed microglial nodules (Fig. 3D). Stain-
ing for glial fibrillary acidic protein (GFAP) re-
veals moderate reactive gliosis (Fig. 3E). Multi-
ple immunohistochemical stains for viruses
(herpes simplex virus, varicellazoster virus,
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of m e dic i n e
cytomegalovirus, and EpsteinBarr virus) are neg-
ative. An immunohistochemical stain for neuro-
nal nuclei shows that the area that was identified
as having features of cortical dysplasia on im-
aging studies has normal cortical architecture
(Fig. 3F).
The two key histopathological findings as-
sociated with cortical dysplasia are disorganiza-
tion of the cortical architecture, with loss of
normal cortical lamination and neuronal cluster-
ing, and the presence of neurons with cytologic
abnormalities, such as irregular shape, large
size, and clumping of Nissl substance.19-21 Other
histopathological features that may be present
are balloon cells and heterotopic neurons in the
white matter and in the cortical molecular layer.22
None of these features are present in this case.
The histologic features of Rasmussens en-
cephalitis consist of chronic encephalitis with
predominance of T lymphocytes, prominent mi-
croglial activation with microglial nodules, neu-
ronophagia, and gliosis; the disease is also as-
sociated with negative immunohistochemical
stains for known viruses. These findings are not
specific for Rasmussens encephalitis, but in a
patient with unilateral hemispheric atrophy and
intractable seizures, they are consistent with the
diagnosis. Several studies suggest a progressive
course, with early symptoms and signs including
intense inflammation and numerous microglial
nodules and later symptoms and signs including
necrosis, marked gliosis, and neuronal loss with
mild inflammation.23 A coexisting condition
was present in about 10% of patients involved in
a large case series.11,24
Dr. Thibert: On awakening after the surgical
procedure, the patient had expressive speech,
and when he was discharged to rehabilitation
services 8 days later, he was walking with as-
sistance. He was discharged from the hospital
approximately 3 to 4 weeks postoperatively and
seen for follow-up 8 weeks postoperatively, at
which time he also returned to school. His
speech and mood are back to baseline and his
strength continues to improve. Six months after
the operation, he was seizure-free, and clonaze-
pam and dietary therapy had been successfully
tapered off.
The Patients Mother: Two months after the op-
eration, my son wanted to go on a half-mile hike
to a fire tower in New Hampshire. I said, Can
 case records of the massachuset ts gener al hospital
you do it? and he said, Yes. We put a bicycle
helmet on him, in case he fell on the uneven
terrain because of the orthosis for his ankle and
foot. He now talks about his Wahoo! moment
he made it to the top of the fire tower. He
wanted to know where Boston was, and you
could look right down and see the city. He took
a picture. When we were coming down, I had to
support him because his legs were shaking so
badly, but he said, Im not quitting yet. So, hes
doing great.
Dr. Duhaime: The patient followed the typical
course of recovery after hemispheric disconnec-
tion, with gradual improvement in language
function, spastic hemiparesis with resumption
of ambulation, and return to baseline arm
strength. Most important, his personality and
sense of humor were preserved, and the disease
can be expected to stop progressing, with con-
tinued improvement over time as the intact
hemisphere consolidates functional control. At
his last follow-up, 2 years after the operation, he
was not taking any medications and was seizure-
free. He has right-sided homonymous hemi-
anopsia and moderate spastic hemiplegia but is
able to walk, run, climb, and bike and is taking
cello lessons.
Dr. Nancy Lee Harris (Pathology): Are there any
questions or comments?
Dr. Kevin Staley (Neurology): Did you consider
continuing therapy with intravenous immune
globulin? It looks as if the patient had a pretty
good response to the therapy initially.
Dr. Thibert: No, the intravenous immune glob-
ulin had lost its effectiveness over time. At the
initial visit, the patient himself actually asked us
to do the surgery.
Dr. Andrew J. Cole (Neurology): I was honored to
be able to work with Dr. Rasmussen when I was
a resident, and I saw a number of his patients. I
think one of the differences between this case
and classic cases of Rasmussens encephalitis is
the remarkably short duration of illness. In this
case, the time between the initial onset of symp-
toms and surgery was approximately 2 years,
whereas in most of the cases that Dr. Rasmussen
encountered, the disease had already undergone
many years of evolution. I suspect that is the
reason why the progressive atrophy was less
striking in this patient than in the patients de-
scribed in historical reports.
n engl j med 371;18nejm.orgoctober 30, 2014
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A major mystery that Dr. Rasmussen empha-
sized was that the inflammatory process begins
unilaterally but also has the propensity to cross
the midline. The likelihood of eventual bilateral
involvement is unclear, but the fear of progres-
sion has been one important driver of early
surgery to try to avoid that evolution.
Finally, Dr. Rasmussen recognized that al-
though the histopathology of the disease is in-
flammatory, the cause is unknown, and it still
remains unclear whether the primary process is
viral, autoimmune, or genetically determined.
Dr. Duhaime: I agree that this is one of the
most mysterious diseases I have treated. I am
struck by the similarities between the unilateral
brain atrophy in patients with Rasmussens en-
cephalitis and in some infants with subdural
hematoma. Both conditions are characterized by
continuous or frequent seizure discharges and
by near-total destruction of one hemisphere with
potentially near-complete preservation of the
contralateral hemisphere. After hemispheric dis-
connection is performed to treat either condi-
tion, the affected hemisphere is still seizing, but
the confinement of the seizures somehow con-
trols symptoms and keeps the disease from pro-
gressing. This feature probably has implications
for the pathogenesis of both disorders that we
do not yet fully understand.
Dr. Harris: Why does a ketogenic diet help to
control seizures?
Dr. Thibert: We do not know exactly why the
diet works, although it has been around for 100
years. The diet mimics starvation; basically, the
body receives foods that are high in fat and low
in carbohydrates, and the brain uses the fatty
acids as its fuel source. It is a very helpful treat-
ment, and in this case, it was the only thing that
was helping to control the patients seizures
before he underwent surgery.
A nat omic a l Di agnosis
Chronic meningoencephalitis consistent with
Rasmussens encephalitis.
This case was presented at Neurology Grand Rounds.
No potential conflict of interest relevant to this article was re-
ported.
Disclosure forms provided by the authors are available with
the full text of this article at NEJM.org.
We thank Dr. Thomas Byrne for assistance with organizing
the conference.
1745
 case records of the massachuset ts gener al hospital

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