Headaches and Pineal Cystshead_1652666..668
Randolph W. Evans, MD; Mario F. Peres, MD
Pineal cysts are common incidental imaging
findings that may be associated with primary
This is a 27-year-old man with migraines without
aura for about 15 years that have increased in fre-
quency to about twice a week in the last 1 year. The
headaches are relieved within 1 hour by a triptan.
Neurological examination was normal.Family history
reveals that both parents,his brother,and sister are all
migraineurs.A magnetic resonance imaging (MRI) of
the brain obtained at the patient’s request revealed a
6-7 mm pineal cyst without mass effect.
Questions: What is the natural history of pineal
cysts? When are follow-up MRI scans indicated? Are
pineal cysts associated with migraines?
Pineal cysts are benign lesions found in up to
2.6% of adults.1Asymptomatic pineal cysts are
usually an incidental neuroimaging finding. Their
main importance is in their differentiation from a
normal cystic component of the gland, from a true
pineal cyst (5 mm or larger in diameter) or cystic
tumors such as germ cell tumors (GCTs), pineal
parenchymal tumors (PPTs),low-grade astrocytomas,
The natural history of pineal cysts is typically
benign. The majority of pineal cysts are silent, and
remain so for years; some may even spontaneously
collapse. In 1 report of 32 patients with pineal cysts
who underwent serial MRIs, 75% of cysts remained
stable over time, while 16% decreased in size or
regressed completely; only 8% increased in size.3In
another study of 26 patients with incidentally found
indeterminate pineal lesions ranging from probable
benign cysts to pineal masses with follow-up MRI
imaging from 7 months to 8 years, all lesions were
stable over time.4In a third study of 106 children and
young adults with pineal cysts followed for a mean
interval of 3.0 years,98 had no increase in size and no
change in imaging appearance, 6 increased in size,
and 2 others had a change in imaging characteristics
without associated growth.The mean age of patients
with cysts that changed or grew was 5.5 years.5The
authors of both studies suggest that pineal cysts can
be followed clinically rather than with serial imaging.
However, the preference for follow-up imaging of
individual clinicians and patients may vary.
Three principal histologic types account for most
tumors arising within the pineal gland: GCTs (38-
69% of pineal tumors), PPTs (pineocytomas and
pineoblastomas, 14-27%), and astrocytomas (12-
27%).6Meningiomas, teratomas, and lipomas may
On MRI, pineal cysts are typically sharply delin-
eated ovoid-shaped lesions, without intracystic trabe-
culations. They have low signal intensity on both T1
and T2, and contrast enhancement is usually nodular
Case Submitted by: Randolph W. Evans, MD, 1200 Binz no.
1370, Houston, TX 77004, USA.
Expert Opinion by: Mario F. Peres, MD, Instituto Israelita de
Ensino e Pesquisa Hospital Albert Einstein, Al Joaquim
Eugenio de Lima, 881 cj 708, 01403-001, Sao Paulo, Brazil.
Published by Wiley Periodicals, Inc.
© 2010 the Authors
Journal compilation © 2010 American Headache Society
and irregular.Like pineal cysts,pineocytomas may be
isointense with cerebrospinal fluid (CSF), but they
usually have intratumoral trabeculations.7On com-
puterized tomography, pineal cysts are hypodense
with respect to CSF, and occasionally there is evi-
dence of recent intra-cyst hemorrhage.Cyst walls may
or may not show contrast enhancement, and calcifi-
cations within the wall are found in about one-half of
Radiologic differential diagnosis with other
pineal gland masses is made more commonly by MRI.
invade through the third ventricle wall,but expansive
compressions are more common with PPTs, low-
grade astrocytomas,and meningiomas.Imaging alone
is not reliable enough to predict histology. In sus-
pected cases, a biopsy should be performed.
Cysts and calcifications are present in up to one-
half of PPT cases, with peripheral calcifications more
suggestive of pineocytoma than germinoma. Benign
pineal cysts may present similarly.
Cystic areas are common,and may be multiple in
GCTs.Calcifications can be identified in two-thirds of
pineal gliomas. Low-grade pilocytic astrocytomas
may be cystic, and unlike other low-grade gliomas,
they enhance with contrast.7
Pineal cysts are benign and asymptomatic lesions.
Symptomatic pineal cysts are usually larger than
those found incidentally. The incidence of symptom-
atic pineal cysts is highest in young women between
21 and 30 years of age, leading to the hypothesis that
hormonal influences contribute to their etiology.1
Symptoms may be caused by aqueductal compression
resulting in hydrocephalus, obstruction of the vein of
Galen, or compression of the collicular plate leading
to Parinaud’s syndrome.
Peres et al described 5 cases of primary head-
aches associated with pineal cysts and suggested that
pineal cysts could be related to headache disorders
not because of compression but abnormal secretion
of the pineal hormone melatonin.8Seifert et al9
studied 51 pineal cysts patients compared with 51
controls. Pineal cyst patients had 2-fold more head-
aches than controls (51% vs 25%).The most common
diagnosis in pineal cysts patients was migraine in 26%
including the 14% with migraine with aura. One
patient had hemicrania continua.
The authors suggest pineal cysts may be related
to headaches,particularly migraine.Interestingly,cyst
diameter was not different in patients with headache
as compared with those without headache. This
finding supports the idea of Peres et al8that melato-
nin dysfunction may be the main mechanism related
to the headache. Melatonin has been linked exten-
sively to headache disorders with experimental and
clinical evidence.10-15Unfortunately, to date, no mea-
sures of melatonin secretion have been performed in
pineal cysts patients.
It is important to look for clinical symptoms
related to pineal and melatonin secretion dysfunction
such as insomnia, delayed sleep phase syndrome, and
desynchronoses in pineal cysts patients. If those signs
are present, a melatonin dysfunction is probably
Small, asymptomatic pineal cysts require no
therapy. If they become symptomatic from hydro-
cephalus, surgical options can be considered.
Melatonin has been studied as a treatment for
headache disorders.Migraine,cluster headache,head-
aches secondary to delayed sleep phase syndrome,
and hypnic headache have all shown to benefit from
melatonin supplementation with minimal side effects.
The patient with a headache disorder and a pineal
cyst may be treated preventively with melatonin start-
ing with 3 mg at bedtime and increasing to 15 mg.10
Melatonin analogs including ramelteon and agomela-
tin may also be helpful but further studies are needed
to confirm their role in headache patients. Sleep
hygiene, sun, daylight exposure, or light therapy may
also be used.
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