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The

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case records of the massachusetts general hospital


Founded by Richard C. Cabot
Nancy Lee Harris, m.d., Editor
Eric S. Rosenberg, m.d., Associate Editor
Jo-Anne O. Shepard, m.d., Associate Editor
Alice M. Cort, m.d., Associate Editor
Sally H. Ebeling, Assistant Editor
Christine C. Peters, Assistant Editor

Case 38-2009: A 16-Year-Old Boy with


Paroxysmal Headaches and Visual Changes
Steven D. Brass, M.D., M.P.H., Marc J. Dinkin, M.D., Ziv Williams, M.D.,
Kalpathy S. Krishnamoorthy, M.D., William A. Copen, M.D.,
and Stefanie H. Freeman, M.D.

Pr e sen tat ion of C a se


A 16-year-old boy was seen in the pediatric neurology clinic of this hospital because
of paroxysmal headaches and visual changes.
The patient had been well until approximately 4 months earlier, when severe headaches began to occur up to three times per month, lasting 3 hours to 8 days (usually 1 to 2 days), and improving with tablets containing a combination of acetaminophen, aspirin, and caffeine. His pediatrician prescribed sumatriptan orally and by
means of a nasal spray. Three days before this evaluation, his father brought him
to the emergency department of this hospital because of a severe headache that
did not respond to sumatriptan. Magnetic resonance imaging (MRI) of the brain
after the administration of gadolinium was normal. His pain improved; he was discharged home and referred to the pediatric neurology clinic of this hospital.
On evaluation in the clinic, the patient described the headaches as pounding and
rated the pain as 5 to 7 on a scale of 1 to 10, where 10 is most severe. They began
in the back of the head and extended to the forehead; were associated with dizziness, nausea, neck pain, and mosaic vision; and were typically relieved by sleep. He
did not have difficulty sleeping, motion sickness, or abdominal pain. He reported
no stress and could not identify triggers for the headaches. He had recently had
sinusitis, for which he had taken amoxicillinclavulanic acid, fluticasone nasal spray,
loratadine, and pseudoephedrine.
Birth and development had been normal. The patient had no known allergies. He
was a good student and had been a competitive athlete but had curtailed physical
activity because of the headaches. He lived with his family. He did not smoke, drink,
or use illicit drugs. He had not traveled recently. His father had had a transient ische
mic attack at the age of 45 years and had headaches and hyperlipidemia; his
mother had diabetes mellitus and was ill from complications of the disease; his
brother was healthy. There was no family history of migraine.
On examination, the vital signs were normal. The pupils were round and reactive to light. The optic-disk margins were sharp, and the visual fields were normal.
The neck was supple, and the remainder of the physical and detailed neurologic
examination was normal. Administration of atenolol was begun. Five weeks later,

From the Departments of Neurology


(S.D.B., K.S.K.), Neuro-Ophthalmology
(M.J.D.), Neurosurgery (Z.W.), Radiology
(W.A.C.), and Pathology (S.H.F.), Massachusetts General Hospital; and the Departments of Neurology (S.D.B., K.S.K.),
Neurology (M.J.D.), Surgery (Z.W.), Radiology (W.A.C.), and Pathology (S.H.F.),
Harvard Medical School.
N Engl J Med 2009;361:2367-78.
Copyright 2009 Massachusetts Medical Society.

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an electroencephalogram (EEG) revealed continuous focal slowing in the right hemisphere over the
posterior regions, with no epileptic activity. Administration of valproic acid was begun.
During the next 6 months, the headaches
gradually resolved, but 6 months later, they recurred daily. The patient rated their severity as 8 to
9 on a scale of 1 to 10; they were preceded at times
by a bubbling feeling in his neck and were associated with nausea and vomiting. On several
occasions, his body stiffened and then went limp,
while his eyes remained open and staring; this
was followed by recovery within 30 seconds. An
EEG showed mild, diffuse background slowing
and superimposed intermittent posterior slowing,
with right-sided predominance and no seizure activity. The serum prolactin level was 25.6 ng per
milliliter (reference range, 0.0 to 15.0). MRI of the
brain was again normal. Magnetic resonance angiography (MRA) of the head and neck and computed tomographic angiography (CTA) showed no
abnormalities. Ophthalmologic ultrasonography
was normal.
During the next 3 years, the patient was seen
in the emergency department of this and other
hospitals multiple times; he was repeatedly admitted to the hospital for headaches associated
with visual changes, nausea, and occasionally leg
cramps. Therapy included intravenous fluids, narcotic analgesics, valproic acid, and ondansetron
for the acute episodes; trials of atenolol, nortriptyline, amitriptyline, gabapentin, butalbital, cyproheptadine, topiramate, and riboflavin for prophylaxis; and other medications (ibuprofen, naproxen,
zolmitriptan, frovatriptan, and sumatriptan tablets and nasal spray) for abortive therapy, which
he used with variable adherence. He saw a psychologist and had some improvement with biofeedback techniques.
When the patient was between 19 and 20 years
of age, episodes of syncope, weakness, and difficulty standing occurred with the headaches, and
the pain radiated to the neck and upper back. Repeated physical, neurologic, and ophthalmologic
examinations disclosed no abnormalities. At 20
years of age, he described photopsias (the sensation of perceiving lights or colors) and partial loss
of vision in the right peripheral visual field. On
evaluation by an ophthalmologist, bilateral opticdisk edema and splinter hemorrhages were seen.
In the emergency department of this hospital,
examination revealed bilateral blurred optic-disk
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margins. MRI, MRA, and magnetic resonance


venography (MRV) of the brain were normal.
A lumbar puncture was performed. The opening
pressure was 11 cm of water (reference range, 6 to
20). Results of cerebrospinal fluid (CSF) analysis
are shown in Table 1. Flow cytometry revealed
normal lymphocytes. The symptoms improved,
and 1 week later, neuro-ophthalmologic examination at this hospital was normal. The complete
blood count; serum levels of electrolytes, magnesium, free thyroxine, thyrotropin, prolactin, insulin-like growth factor 1, norepinephrine, dopamine,
epinephrine, normetanephrine, and metanephrine;
and the level of 5-hydroxyindoleacetic acid in a
timed urine specimen were normal.
When the patient was 20 years 10 months of
age, low back pain and transient inability to move
or respond occurred during a severe headache. In
the emergency department, he was most comfortable sitting forward with his head down. CT of
the head showed no evidence of hemorrhage, and
he declined lumbar puncture. Neurologic examination, including funduscopic examination, was
normal. Narcotic analgesia was given, with improvement. MRI of the spine was ordered, but the
patient returned to college without undergoing
the study.
When the patient was 21 years of age, severe
headaches associated with pain in the shoulder
and low back, visual changes, and loss of consciousness occurred three times in 1 week (once
with incontinence). He was admitted to the neurology service of this hospital for video EEG
monitoring. On examination, there was bilateral
optic-disk edema; the vital signs and the remainder of the examination were normal. The complete blood count, serum electrolyte levels, and
tests of liver and renal function were normal.
On the second hospital day, during a severe
headache, the patient reported numbness in his
groin and perineum and sensory loss down the
back of his left leg and heel, which resolved in
10 minutes. Neurologic examination and MRI and
MRV of the brain were normal. He remained in
bed, crouched on his elbows and knees, moaning, until morphine was administered. EEG during the headache showed theta-range slowing of
the background, most prominent over the temporal regions. On the third day, neuro-ophthalmologic evaluation revealed elevated optic disks
with blurred margins (more blurred on the left
than the right), obscuration of the vessels at the

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Table 1. Cerebrospinal Fluid Analysis.


Reference Range,
Adults*

Variable

Color

Colorless

Age of Patient
20 Yr 1 Mo

21 Yr 1 Mo,
5th Hospital Day

Colorless

Colorless

Turbidity

Clear

Clear

Clear

Xanthochromia

None

None

None

Tube 1

1667

202

Tube 4

1244

92

Tube 1

05

Tube 4

05

Neutrophils

28

Lymphocytes

68

72

28

555

47

32

Red cells (per mm3)

White cells (per mm3)

Differential count (%)

Monocytes
Protein (mg/dl)
Glucose (mg/dl)

5075

73

69

Nonreactive

Nonreactive

Nonreactive

Grams stain

No organisms

No organisms

No organisms

Acid-fast bacilli smear

No organisms

No organisms

No organisms

Fungal wet prep

No organisms

Test not performed

No organisms

Routine

No growth

No growth

No growth

Fungal

No growth

No growth

No growth

Mycobacterial

No growth

No growth

No growth

Cryptococcal antigen

Negative

Negative

Negative

Herpes simplex virus (DNA amplification)

Negative

Venereal Disease Research Laboratory test

Cultures

Test not performed, white- Test not performed, whitecell count and protein
cell count and protein
too low
too low

* Reference values are affected by many variables, including the patient population and the laboratory methods used. The
ranges used at Massachusetts General Hospital are for adults who are not pregnant and do not have medical conditions that could affect the results. They may therefore not be appropriate for all patients.
To convert the values for glucose to millimoles per liter, multiply by 0.05551.

disk margins, and a small flame-shaped hemorrhage at the superior nasal margin of the left
optic disk.
On the fifth day, the patient again reported
numbness in the left groin and leg; neurologic
examination was normal. A lumbar puncture was
performed. The opening pressure was 25 cm of
water; results of CSF analysis are shown in Table 1.
Cytopathological examination revealed no malignant cells, and flow cytometry showed normal
lymphocytes. Two hours after the procedure, the
patient felt constipated; he was able to defecate but

reported a lack of rectal sensation. On examination, there was decreased sensation in the area of
the dermatomes of sacral nerves S1 through S4 on
the left and decreased perianal sensation and rectal tone; strength in the legs was normal, but the
left patellar and ankle reflexes were diminished.
A diagnostic procedure was performed.

Differ en t i a l Di agnosis
Dr. Kalpathy S. Krishnamoorthy: On initial evaluation,
when he was 16 years of age, and on several follow-

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up evaluations until he was 19.5 years of age, the


patient had a normal neurologic examination, including the funduscopic examination. He was intelligent, articulate, and seemed to be a reliable
historian. At the time of his first visit, I requested
MRI to rule out mass lesions, hydrocephalus, vascular malformations, and type I Chiari malformation, none of which were detected. He met all
the criteria described by the International Headache Society for migraine without aura, and some
of the criteria for migraine with aura, including
recurrent attacks of bilateral or unilateral throbbing headaches, with visual aura, lasting for hours
and sometimes days, often associated with nausea, vomiting, and photophobia. Migraine is one
of the common causes of headaches in teenagers,
with a prevalence of 4 to 11% among teenagers
who have headaches.1 The onset in boys is usually before puberty, and in girls it is more common at or after puberty, but the age of onset is
not helpful in diagnosis. After an initial response
to valproic acid, this patient had multiple attacks
that were resistant to all prophylactic and rescue
migraine medications. I considered transformed
migraine (also known as chronic migraine) and
mixed headaches.1 In both conditions, progressive
and recurrent migrainous episodes are superimposed on chronic daily headaches. Many patients
have substantial psychosocial stress. Approximately 18% of teenagers with migraines have mixed
headaches.1
Over time, unusual symptoms developed, including transient loss of consciousness, weakness,
obtundation, and lethargy. Some of these features
suggested basilar migraines, which affect the
brain stem, cerebellum, and parieto-occipital regions. Symptoms of basilar migraines include
diplopia, ataxia, vertigo, motor deficits (e.g., hemiparesis and quadriparesis), syncope, vomiting,
lethargy, and obtundation. Some basilar migraines
may mimic strokes or seizures. None of the deficits lasted long enough to make this diagnosis.
As the patients headaches became intractable,
psychosocial stresses were also considered among
the causes. He had started college and was leaving home. His mother had a chronic illness, and
sometimes he seemed depressed and anxious. He
was going to emergency rooms and requesting
morphine, and he had no satisfactory response
to therapy with antimigraine drugs. However, a
psychiatrist did not find evidence of depression
or other psychiatric illness. At one admission,
when he presented with vomiting, flushing, and
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sweating, I considered catecholamine-releasing


tumors or a carcinoid tumor, but the workup was
negative.
My working diagnosis was intractable migraine. The patient was transferred to the adult
neurology service at 19.5 years of age.
Dr. Steven D. Brass: This now 21-year-old man had
recurrent paroxysmal headaches with episodic loss
of consciousness and intermittent bilateral optic-disk edema. Neuroimaging of the brain and
head and neck vasculature on several occasions
did not reveal a mass, an aneurysm, or central
venous thrombosis. An EEG showed no epileptiform activity. We requested consultation with
neuro-ophthalmology to assess whether his optic-disk abnormality was in fact papilledema.
Dr. Marc J. Dinkin: The differential diagnosis of
optic-disk edema, when it is referred to as a papillitis, includes ischemia, compression, and infiltration and inflammation of the anterior optic nerve.
Such cases are characterized by decreased visual
acuity, dyschromatopsia, an afferent pupillary defect, and arcuate, central, or centrocecal scotomas,
whereas transient visual obscurations are rare. Increased intracranial pressure tends to cause bilateral optic-disk edema, called papilledema, and
papilledema may result from stasis of axoplasmic
transport down the nerves, secondary to increased
intracranial pressure.2 The visual symptoms and
signs of papilledema differ from those of other
types of optic-disk edema in that acuity and color
vision are typically preserved until the late stages,
as they were in this case. The preservation of acuity, color vision, central field, and papillary function all result from the relative sparing of the
maculopapillary bundle (axons leading from central macular ganglion cells to the optic nerve) in
early papilledema. Transient visual obscurations,
which our patient had, are also more common
with papilledema, occurring in 68% of patients,3
and may result from transient ischemia to the
nerve in the context of high intracranial pressure
and changes in position.4 The temporal scotoma
in his right eye that we observed reflected the enlarged physiological blind spot of papilledema,
which results from the presence of peripapillary
fluid between the retina and retinal pigment epithelium.5,6
When the patient was first seen by our neuroophthalmology service, disk edema had been
observed a week earlier; however, his optic disks
were normal on our examination. A lumbar puncture performed between the examinations showed

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a normal opening pressure. A year later, when he


was seen closer to the time of a headache, his optic
nerves showed many signs of papilledema, including elevation of the edge of the disks, venous distention, and one splinter hemorrhage (Fig. 1A).
A subsequent lumbar puncture showed increased
intracranial pressure.
The finding of papilledema helped identify increased intracranial pressure as the cause of the
patients symptoms, but its sporadic nature led to
a delay in the diagnosis. In experiments in nonhuman primates, papilledema developed as early
as 24 hours after an increase in intracranial pressure7; in studies in humans, papilledema typically
develops only after several days of elevated intra
cranial pressure.8 Papilledema may resolve within 2 weeks after abrupt normalization of intracranial pressure,3,9 whereas in medically treated
patients with idiopathic intracranial hypertension,
it resolves at an average of 5 months.10 Thus, the
fleeting nature of the papilledema in this patient
suggested the presence of paroxysmal, short-lived
elevations in intracranial pressure.
Dr. Brass: Of the many disorders that can pre
sent with headache and papilledema,11,12 I focused
my differential diagnosis on idiopathic intracranial hypertension, vascular causes, infectious diseases, and a central nervous system neoplasm as
the most likely possibilities.

Idiopathic Intracranial Hypertension

Idiopathic intracranial hypertension was initially


the leading diagnosis. This condition typically
occurs in overweight adolescent girls and young
women.11-13 An unremitting headache with episodic worsening is accompanied by pulsatile tinnitus, transient visual obscuration, and diplopia.
Visual acuity is preserved until late in the course
of the disease. Examination often shows bilateral
disk edema. The diagnostic criteria include a normal cranial MRI and MRV and an opening pressure on lumbar puncture greater than 25 cm of
water, with a normal CSF composition.11 Most of
the reported neuroimaging signs on cross-sectional
imaging are not helpful in establishing or ruling
out this diagnosis.14 Treatment includes weight
reduction, lowering the intracranial pressure with
acetazolamide, and surgical treatment with either
fenestration of the optic-nerve sheath or lumbarto-peritoneal shunting.11-13 Because of a high suspicion for this diagnosis, I started treatment with
acetazolamide after the lumbar puncture. How-

Figure 1. Funduscopic Examination.


On funduscopic examination during the current admission (Panel A), there
is hyperemia ofICM
the nasal
disks and
blurring of the nasal
margins,
RETAKE
1st as well as
Brass
AUTHOR
a splinter hemorrhage.
Examination
3
months
after
the
first
operation,
at
2nd
REG F FIGURE
1a&b
3rd
the time of recurrent
symptoms (Panel B), discloses persistent
veCASE visual
TITLE
Revised
nous dilatationEMail
(arrowhead), a tortuous artery (white arrow),
and severe
4-C
Line
360-degree swelling
the optic-nerve
head
(black
arrow),
features consisSIZE
Enon ofARTIST:
mst
H/T
H/T
22p3
tent with worsening
FILL papilledema.
Combo
AUTHOR, PLEASE NOTE:
Figure has been redrawn and type has been reset.
Please check carefully.

ever, arguing against this diagnosis was the fact


36124 paroxysmal, asISSUE:
12-10-09
JOB: were
that his headaches
was his
disk edema, unlike the chronic findings reported
in cases of this condition. In addition, he was thin
and male, features atypical for this condition.

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Figure 2. Images of the Spine.


Sagittal T2 -weighted (Panel A) and T1-weighted (Panel B) MRIs show a cystic-appearing mass lesion that nearly fills
the sacral canal, compressing the sacral nerve roots. An axial T2 -weighted image of the sacrum (Panel C) shows a
1st
Brass the left S2S3RETAKE
AUTHOR through
ICM protruding
bulbous component of the sacral mass
anterior sacral
foramen. The urinary blad2nd
REG from
F FIGURE
2a-f
der is distended. Reformatted images
a CT myelogram
(Panel D) show an absence
of visible injected contrast
3rd
CASE
material in most of the lesion, confirming
that there is no wide-open communication
with the thecal sac, but a
TITLE
Revised
small quantity of contrast material EMail
seen in the bulbous sacral
4-Cof the cyst (Panel E, arrow) confirms that
Lineportion
SIZE
Enon
ARTIST: mst
some communication is present. Surface
rendering
produced
H/Tmyelogram images (Panel F) shows spinal
H/Tfrom CT
33p9
FILL
Combo
dysraphism with congenital nonfusion
of the posterior sacral
elements (arrows).

Vascular causes

AUTHOR, PLEASE NOTE:


Figure has been redrawn and type has been reset.
Please check carefully.

Cerebral venous thrombosis may


present with an
JOB: 36124
acute onset or chronic progressive headache,
papilledema, transient visual symptoms, seizures,
focal neurologic signs, or subacute encephalopathy, depending on the location and extent of the
thrombus.15,16 MRI will show evidence of infarct,
hemorrhage, or thrombosis, and there may be a
lack of signal on MRV.17 Our patients presenta2372

tion of paroxysmal headache and papilledema,


with completely
asymptomatic intervals and norISSUE: 12-10-09
mal examinations between episodes, and normal
MRV ruled out this diagnosis.

Meningitis

Recurrent meningitis may cause intermittent meningeal symptoms and CSF abnormalities, followed
by periods of normal clinical and CSF findings.18-20

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Patients may have recurrent headache, fever, nausea, change in mental status, nuchal rigidity, seizures, focal neurologic findings, cranial-nerve palsies, and papilledema.21 Examination of the spinal
fluid reveals an elevated opening pressure with
pleocytosis, normal or elevated protein levels, and
a variable glucose level, depending on the cause.
MRI may show meningeal enhancement. Our patient had no fever or meningismus, repeated neuroimaging did not show meningeal enhancement,
and repeated CSF examinations did not support
this diagnosis.18-20
Central Nervous System Neoplasm

Brain tumors may present with headaches, and


headaches occur in 60% of patients who have brain
tumors.22,23 The headaches are usually worse during a Valsalva maneuver and on wakening, probably because of increases in intracranial pressure.
Headaches may be migraine or tensionlike and
may be accompanied by papilledema, focal neurologic findings, nausea, or seizures. When headaches are paroxysmal and associated with vomiting, visual symptoms, drop attacks, and loss of
consciousness, one must consider that a neoplasm,
such as colloid cyst of the third ventricle, may be
causing intermittent hydrocephalus.24 Other intraventricular or periventricular tumors, such as
pinealoma, craniopharyngioma, and ependymoma,
should also be considered.25 In this patient, multiple cranial MRIs ruled out an intracranial tumor.
Patients with spinal cord tumors such as
ependymomas and neurofibromas may on rare
occasions present with headache and papilledema as the initial symptoms, although typically
when headache and papilledema develop in a patient with a spinal-cord neoplasm, spinal symptoms have already evolved.26-31 It has been suggested that a spinal cord tumor may lead to
mechanical and physiological changes in both CSF
absorption and flow, causing a rise in intracranial pressure.26-31 Our patients spinal symptoms
were not initially prominent, and his normal examination indicated that a spinal tumor was unlikely. However, during the year before this admission, low back pain developed; during this
admission, he described numbness of the left groin
and leg, and several hours after the lumbar puncture, neurologic deficits indicating compression
of the spinal cord or thecal sac developed, suggesting the presence of an intraspinal mass. Imaging
studies were obtained.
Dr. William A. Copen: T2-weighted MRI of the lum-

Figure 3. Biopsy Specimen of the Cyst Wall.


There is a fibrous connective-tissue wall with a thin, flattened arachnoid cell lining and an arachnoid granulation
RETAKE
1st
AUTHOR Brass
ICM A, hematoxylin
(Panel
and eosin). Immunohistochemi2nd
F FIGURE
3a&b membrane antigen highlights
cal REG
staining
for epithelial
3rd
CASE
TITLE lining of the cyst (Panel B,Revised
the thin epithelial
immuEMail
Line membrane
4-C
noperoxidase
stain for epithelial
antigen).
Enon

ARTIST: mst

FILL

H/T
Combo

H/T

SIZE
16p6

AUTHOR, PLEASE NOTE:

bar spine
(Fig.
2A)redrawn
reveals
hyperintense
Figure
has been
and a
type
has been reset. extraPlease check carefully.
dural mass that nearly
fills the sacral canal, markedly JOB:
compressing
the sacral-nerve
roots. The mass
36124
ISSUE: 12-10-09
is markedly hypointense on T1-weighted MRI and
has no enhancing components (Fig. 2B), suggesting a cyst. Expansion of the sacral canal, with deep
scalloping of the bodies of the sacral segments,
indicates a chronic, gradually expanding cyst.
A bulb-shaped component extends through and
expands the left S2S3 anterior sacral foramen
(Fig. 2C), suggesting a perineural cyst arising from
the sheath of the left S2 nerve root.
A sagittal reformatted image from a CT myelogram (Fig. 2D) shows injected contrast material
in the subdural space and the thecal sac but not
within the cyst, indicating that the wide-open
communication between the thecal sac and the
cyst that would be expected in a meningocele or
pseudomeningocele is missing. However, a left
parasagittal image (Fig. 2E) shows contrast lay-

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ering in the portion of the cyst within the left


S2S3 anterior sacral foramen, indicating some
communication between the cyst and the thecal
sac and suggesting that the cyst may have arisen
from the nerve-root sheath at this level. However,
enlargement of a perineural cyst to this size within the sacral canal would be unusual. A surface
rendering of the CT myelogram images (Fig. 2F)
shows nonfusion of the sacral posterior elements,
indicating occult congenital spinal dysraphism.
This abnormality has been reported in association
with spinal arachnoid cysts, making this the most
likely diagnosis in this case.32,33
Dr. Ziv Williams: This patient presented with
acute cauda equina syndrome due to compression
of the descending lumbosacral nerve roots by the
cyst. Decompression within 48 hours after symptom onset was necessary to avoid a permanent
neurologic deficit.34 However, the patient also had
chronic symptoms associated with elevated intra
cranial pressure. Two approaches were considered.
Fenestration would provide direct decompression
of the cyst and immediately relieve pressure on
the nerve roots but might not relieve the elevated
intracranial pressure. Diversion of the CSF by
means of a shunt might decrease the intracranial pressure. The CT myelogram showed a small
amount of contrast material within the cyst, but
it was uncertain whether fluid communicated
freely between the subarachnoid space and the
entire cyst. If communication between the cyst
contents and the subarachnoid space was incomplete or inconsistent, shunting might not provide adequate decompression.35
We elected to perform cyst fenestration, with
the option of performing a diversionary procedure for the CSF at a later date, if elevated intra
cranial pressure persisted. By decompressing the
cyst into the subarachnoid space, the pressure
gradient between the two compartments is equilibrated and the pressure on the nerves is relieved.
Either complete excision or wide fenestration with
or without placement of a shunt into the sub
arachnoid space or peritoneum is recommended
to limit the possibility of recurrence.36
In the operating room, a midline incision was
made over the lumbosacral area, and the L4
through S2 lamina were removed. An intraspinal,
extradural cyst protruded through a large dorsal
dural defect extending from the L5 to S1 levels.
The cyst was gray and translucent, consistent in
appearance with an arachnoid cyst. Microdissection was performed intradurally through the de2374

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Figure 4 (facing page). Follow-up Imaging Studies.


Sagittal T2 -weighted MRI of the lumbar spine, obtained
1 month after spinal surgery (Panel A), shows that
mass effect on the sacral nerve roots has increased because of a fluid collection in the operative bed that
may indicate cyst reaccumulation or pseudomeningocele. Two and a half months after the operation (Panel
B), the mass effect has resolved. An axial T2 -weighted
image through the orbits (Panel C), obtained 3 months
after surgery, when the patient was having visual symptoms, shows expansion of the optic-nerve sheaths
(short arrows), kinking of the optic nerves (long arrow), and concavity of the globe at the insertion of the
right optic nerve (arrowhead), features that indicate increased intracranial pressure.

fect, and the cyst wall was widely removed. The


descending nerve roots appeared to be displaced
ventrolaterally and did not traverse the cyst cavity.
Some of the cyst that was adherent to the nerve
roots was left behind. A lumbosacral fascial graft
was used to close the dural defect.

Cl inic a l Di agnosis
Spinal arachnoid cyst.

Pathol o gic a l Discussion


Dr. Stefanie H. Freeman: A portion of the cyst wall was
submitted for histopathological examination. It is
composed of fibrous connective tissue with a thin
lining composed of flattened epithelial cells, consistent with an arachnoid cyst (Fig. 3A). Immunohistochemical staining for epithelial membrane
antigen highlights the thin epithelial lining of the
cyst (Fig. 3B). The differential diagnosis of spinal
cysts includes ependymal cysts (which are composed of cuboidal to columnar ciliated cells and
may resemble the ependymal lining), dermoid and
epidermoid cysts (which have a keratinizing, stratified, squamous epithelium and contain keratin
debris), and enterogenous cysts (which have a lining of well-differentiated cuboidal to columnar
epithelium and may contain mucin or have cilia).37
The findings in this case are consistent with the
diagnosis of an arachnoid cyst.
Arachnoid cysts may be intradural or, more
commonly, extradural.38 The cause is unknown,
but most extradural cysts are associated with a
defect in the dura that is presumed to be congenital, as in this case.38-40 Meningeal cysts can be
classified on the basis of their location.41 Type I
cysts are extradural, without involvement of nerve-

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root fibers. Type II cysts are extradural but inDiscussion of M a nagemen t


volve nerve-root fibers (Tarlov perineurial cysts),
Dr. Brass: After
the operation,
the patients neuroand type III cysts are intradural.
TheAUTHOR
cyst in this
RETAKE
1st
Brass
ICM
logic
symptoms
resolved
and
his
paroxysmal headcase would be classified as type
I.
2nd
REG F FIGURE 4a-c
3rd

CASE

TITLE
Revised
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j med 361;24 nejm.org
10, 2009
4-C
Line december
SIZE
Enon
ARTIST: mst
H/T
H/T
The New England
Journal of Medicine
33p9
FILL
Combo
EMail
engl

Downloaded from nejm.org on May 7, 2013. For personal use only. No other uses without permission.
AUTHOR, PLEASE NOTE:
Copyright
2009
Massachusetts
All rights reserved.
Figure
has been
redrawn andMedical
type has Society.
been reset.
Please check carefully.

2375

The

n e w e ng l a n d j o u r na l

of

m e dic i n e

A
Epidural
space

Subarachnoid
space

B
Nerve root
Dura

Subarachnoid
space
Arachnoid

S1
Slit valve
opening

Ilium

Cyst
Nerve roots

L5

S1

Subarachnoid
space
Cyst
Cyst

S2

Figure 5. Diagram of the Spinal Arachnoid Cyst and Its Possible Effect on the Flow of Cerebrospinal Fluid (CSF).
COLOR FIGURE
The cyst was located in the subarachnoid space and protruded through a small defect in the dura, compressing the lumbosacral nerve
Rev3
11/18/09
roots (Panel A). There are several possible explanations for the associated increased intracranial pressure. First, the cyst may have
produced
a mass effect on the subarachnoid space. Second, its presence may have led to a reduction in the surface
area of arachnoid
granulations in
Author
Dr. Brass
that region and therefore a reduction in the absorption of CSF. A third theory specifically addresses the presence
of paroxysmal
spikes in
Fig #
5
intracranial pressure associated with changes in position a slitlike opening in the cyst could have acted
as a valve, resulting in intermitTitle
tent release of cyst fluid into the subarachnoid space. (Panel B, arrow), with consequent sudden increases
MEin intracranial pressure. After
partial removal of the cyst wall, the slit valve would have been removed, but the open connection between the subarachnoid space and a
Phimister
DE
developing pseudomeningocele (Panel C, arrows) may have further reduced the capacity of spinal arachnoid granulations to absorb CSF,
Muller
Artist
leading to a more protracted (although milder) state of high intracranial pressure that was necessary for the emergence of chronic papilleAUTHOR PLEASE NOTE:
dema and associated visual-field changes.
Figure has been redrawn and type has been reset
Please check carefully

aches ceased. However, he now described a persistent low-grade (1 on a scale of 1 to 10) headache.
Three months postoperatively, he reported translucencies in his vision.
Dr. Dinkin: Neuro-ophthalmologic examination
revealed worsening papilledema, with hemorrhage (Fig. 1B), and on visual-field testing, there
was a constriction of the inferior nasal visual field,
reflecting damage to the retinal nerve-fiber layer,
which occurs with chronic papilledema and tends
to affect the superior fibers.42
Dr. Copen: A sagittal T2-weighted image of the
lumbar spine approximately 1 month after spinal
surgery (Fig. 4A) shows a large fluid collection
extending from the original location of the cyst
through a new multilevel laminectomy defect. It is
unclear whether this represents cyst reexpansion,
a postoperative seroma, or a pseudomeningocele.
Mass effect on the thecal sac has increased since
the preoperative examination. A repeat examina2376

n engl j med 361;24

tion performed 6 weeks later12-10-2009


(Fig. 4B) shows the
resolution of mass effect on the thecal sac.
An axial T2-weighted image through the orbits
obtained 3 months postoperatively, at the onset
of new visual symptoms (Fig. 4C), shows marked
expansion of the optic-nerve sheaths bilaterally
and kinking of the optic nerves, reflecting increased intracranial pressure. There also appears
to be slight concavity of the globe at the insertion
of the optic nerve, a feature that suggests papilledema.
Dr. Dinkin: This case is unusual in that although
fenestration of the cyst led to remission of the
paroxysmal headaches, it also resulted in longstanding papilledema associated with significant
visual-field defects. The operation may have removed a slit-valve mechanism between the cyst and
the subarachnoid space, preventing further abrupt
fluid shifts and elevations in the intracranial pressure (Fig. 5). However, the open connection be-

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tween the subarachnoid space and a developing


pseudomeningocele may have reduced the capacity
of spinal arachnoid granulations to absorb CSF,
leading to a more protracted (although milder)
state of high intracranial pressure necessary for
the emergence of chronic papilledema and associated visual-field changes.
Dr. Williams: To relieve the increased intracranial pressure, we considered performing a lumbarto-peritoneal shunt or a ventricular-to-peritoneal
shunt. The lumbar-to-peritoneal approach is less
invasive, but after the shunt is placed, the rate of
flow cannot be adjusted. The patient also had recent lumbar spinal surgery, and the CSF dynamics leading to his elevated intracranial pressure
were unclear. Placement of a ventricular-to-peritoneal shunt is a more invasive procedure, with a
higher likelihood of complications, but the rate
of flow can be modified with the use of a valve
that can be controlled with an external magnet.
Depending on the patients symptoms, the shunt
can be adjusted to provide greater or lesser flow
through the catheter. This was an important consideration in this case, since we did not know how
the patients symptoms would respond to CSF diversion. We elected to place a ventricular-to-peritoneal shunt; the procedure was performed without complications.
Dr. Brass: After placement of the shunt, the patients headaches, papilledema, and retinal hemorrhages resolved. In retrospect, it is clear that
elevated intracranial pressure caused his signs and
symptoms. Spinal arachnoid cysts are rare in children, with fewer than 40 cases reported, and they
are rarely associated with elevated intracranial
pressure.32,38,43-46 It has been postulated that spinal arachnoid cysts may develop as a result of elevated intracranial pressure or that these cysts may
cause elevated intracranial pressure by means of
a mass effect on the thecal sac. The thecal sac

normally expands and responds to physiologic


changes in CSF volume without causing appreciable changes in pressure. The mass effect of a spinal lesion may affect this distensibility, ultimately
leading to an elevation in intracranial pressure.
The slitlike valve between the cyst and the sub
arachnoid space may explain the paroxysmal
symptoms and postural effects seen in this pa
tient.32,38,43-46
This case serves as an important reminder that
increased intracranial pressure may be caused by
abnormalities outside the cranial cavity. It also
emphasizes the need to continually reassess a patient with atypical symptoms until a diagnosis that
explains all the symptoms is established.
A Physician: Were there any cutaneous manifestations over the base of the spine, such as a hemangioma, that might have suggested the presence of a spinal lesion?
Dr. Williams: I saw no external manifestations.
Dr. Ronald E. Kleinman (Pediatrics): What has
been the emotional effect of this protracted illness on this young man?
Dr. Brass: He missed a lot of school, but he is
well adjusted and is doing well in college. Despite
all that has happened, he is not bitter and has
taken an interest in his case. After the diagnosis
of the spinal arachnoid cyst, he asked me, Do you
think I am going to be in the New England Journal
of Medicine?

A nat omic a l Di agnosis


Spinal arachnoid cyst.
This case was presented at Pediatric Grand Rounds, April 1,
2008.
Dr. Brass reports receiving consulting fees from EMD Serono
and Teva Neuroscience; and Dr. Freeman, holding equity ownership in Abbott Laboratories. No other potential conflict of interest relevant to this article was reported.

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