J Neurol (2012) 259:306310

DOI 10.1007/s00415-011-6181-z

ORIGINAL COMMUNICATION

Second-half-of-the-day headache as a manifestation

of spontaneous CSF leak
Andrea N. Leep Hunderfund Bahram Mokri

Received: 2 May 2011 / Revised: 7 July 2011 / Accepted: 9 July 2011 / Published online: 3 August 2011
Springer-Verlag 2011

Abstract Orthostatic headache related to spontaneous

cerebrospinal fluid leak (CSF) appears within 2 h of sitting
or standing in most patients. However, longer delays to
headache onset have been observed, including some
patients who have headaches only in the afternoon. The
objective of this study is to describe second-half-of-the-day
headache as a manifestation of spontaneous CSF leak and
propose potential mechanisms. From 142 patients evaluated by one of us (B.M.) during a 10-year period for
spontaneous intracranial hypotension, those describing
headache occurring exclusively in the afternoon accompanied by typical changes of intracranial hypotension on
head MRI were retrospectively identified and their medical
records reviewed. Five patients met our pre-defined
inclusion criteria (5/142, 3.5%; three women; mean age
50 years). Second-half-of-the-day headache was an initial
symptom of intracranial hypotension in one patient, spontaneously evolved from prior all-day orthostatic headache
in one patient, and was a residual or recurrent symptom
after epidural blood patch in three patients. Head MRI
changes due to intracranial hypotension were decreased
during second-half-of-the-day-headache compared to typical all-day orthostatic headache in three out of four
patients. The timing of second-half-of-the-day headache
and orthostatic headache in the clinical course of patients
with spontaneous CSF leaks and related MRI findings
suggest that second-half-of-the-day headache is likely a
manifestation of a slowed or slow-flow CSF leak.

A. N. Leep Hunderfund (&)
B. Mokri

Department of Neurology, Mayo Clinic College of Medicine,
200 First Street SW, Rochester, MN 55905, USA
e-mail: leep.andrea@mayo.edu

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Keywords Headache
Intracranial hypotension

Cerebrospinal fluid leak
Orthostatic headache

Low pressure syndrome

Introduction
Headache is the most common clinical manifestation of
spontaneous intracranial hypotension due to cerebrospinal
fluid (CSF) leak. The related headache is typically orthostatic
(present in the upright position, relieved by recumbency),
although other headache types have been recognized. These
include non-orthostatic headache (which may precede or
follow typical orthostatic headache), exertional headache [1],
thunderclap headache at onset before orthostatic features
become apparent [2], non-orthostatic chronic daily headache
[3], orthostatic coat hanger neck and shoulder discomfort
with or without occipital headache [4], or rarely paradoxical
postural headache (present in recumbency, relieved in the
upright position) [5]. While most patients with spontaneous
intracranial hypotension experience headache within 2 h of
sitting or standing [6], others experience longer delays to
headache onset with headache beginning in the late morning
or early afternoon. Such headaches often linger for the rest of
the day with varying degrees of orthostatic features. This
phenomenon has been termed second-half-of-the-day headache [1]. The objective of this study is to draw attention to this
phenomenon, describe the clinical features of such patients,
and propose possible pathophysiologic mechanisms.

Methods
Those patients evaluated by one of us (B.M.) between
January 1, 2000 and December 31, 2009 for spontaneous

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307

Table 1 Clinical characteristics of patients with second-half-of-the-day headache

Patient no./age/sex

Type of second-half-of-theday headache

Timing in clinical course

Associated symptoms

1/51/M

Orthostatic

Residual symptom after three epidural blood patches

for all-day orthostatic headache

Dizziness
Tinnitus and altered hearing
Dysgeusia

2/46/F

Orthostatic

Residual symptom after epidural blood patch for allday orthostatic headache; residual/recurrent
symptom after a second surgical repair and
multiple epidural blood patches

Valsalva headache
Nausea
Altered hearing
Horizontal diplopia
Neck and upper back tightness/pain

3/53/M

4/34/F

5/64/F

Orthostatic

Orthostatic

Constant

Residual symptom after epidural blood patch for allday orthostatic headache, exertional, and Valsalva
headache

Valsalva headache

All-day orthostatic headache that over time

spontaneously evolved into second-half-of-the-day
headache

Altered hearing

Initial symptom, evolved into all-day orthostatic

headache within a few days

Neck tightness/pain

intracranial hypotension due to CSF leak with characteristic findings of spontaneous intracranial hypotension on
gadolinium enhanced head [7, 8] or spine [9, 10] magnetic
resonance imaging (MRI) or clear leak visualized by
computed tomographic (CT) myelography were retrospectively identified via a search of the Mayo Clinic
electronic medical record. From the resulting 142 patients,
those describing headache occurring exclusively in the
second half of the day accompanied by typical changes of
intracranial hypotension on head MRI were selected for
analysis. Head MRI can be normal in patients with spontaneous intracranial hypotension, especially if performed
shortly after symptom onset [11, 12]. We nevertheless
opted to exclude these patients in order to avoid possible
clinical misdiagnoses, since afternoon only or afternoon
predominant headache can be seen in a variety of headache
types. All imaging studies were reviewed by experienced
neuroradiologists familiar with the radiologic manifestations of intracranial hypotension. Basic statistics (mean,
range, percent) were applied. The Mayo Clinic Institutional
Review Board approved this study, and all included
patients consented to the use of their medical records in
research.

Results
Over the designated 10-year timeframe, seven of 142
patients (4.9%) with spontaneous CSF leak described second-half-of-the-day headache. Two of these patients were
excluded because while head MRI did show typical

Exertional headache

Neck tightness/pain

changes of spontaneous intracranial hypotension at other

points in the clinical course of their CSF leaks, these
changes were not present at the time of ongoing
second-half-of-the-day-headache. While a normal head
MRI does not completely rule out ongoing CSF leak, these
patients were nevertheless excluded in order to maintain
strict inclusion criteria. This left five patients (5/142, 3.5%)
with second-half-of-the-day headache accompanied by
typical head MRI changes of spontaneous intracranial
hypotension.
The clinical features and headache characteristics of
each patient are summarized in Table 1. Three of the five
patients were women. Mean age at the time of our evaluation was 50 years (range 3464). All patients were
headache free in the morning, with headache appearing
after mid-day. The second-half-of-the-day headache was a
typical orthostatic headache in four patients and a constant
headache without prominent orthostatic features in one
patient.
Two patients experienced other headache types at the
time of second-half-of-the-day headache. These included
Valsalva and exertional headache in patient 3 and Valsalva
headache in patient 2. Other symptoms experienced by
patients in connection with their second-half-of-the-day
headache included cochleovestibular complaints such as
dizziness, tinnitus, ear fullness, or muffled hearing;
(n = 3), subjective neck stiffness or neck pain (n = 3),
nausea (n = 2), horizontal diplopia due to bilateral cranial
nerve VI palsies (n = 1), and dysgeusia (n = 1). No
patient had a history of migraine headaches. Two patients
had joint hypermobility and hyperextensible skin (patients

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J Neurol (2012) 259:306310

Fig. 1 Head MRI in second-half-of-the-day headache. Top rows

represent initial head MRI during typical all-day orthostatic headache;
bottom rows represent subsequent head MRI during second-half-ofthe-day headache: a mid-sagittal T1-weighted image, b coronal
gadolinium-enhanced T1-weighted image, c axial gadolinium-

enhanced T1-weighted image; patient 2 demonstrated disappearance

of diffuse pachymeningeal enhancement and decreased downward
displacement of the cerebellar tonsils with persistent effacement of
the basilar cisterns and flattening of the ventral pons

2 and 4). A potential precipitating event was present in two

patients prior to onset of symptoms attributed to intracranial hypotension (bending over, patient 2; bowing for
prayers, patient 3).
Timing of second-half-of-the-day headache in the clinical course of patients with spontaneous intracranial
hypotension varied. Patient 5 described second-half-of-theday headache as an initial symptom of spontaneous intracranial hypotension, which over time progressed into
typical all-day orthostatic headache. Patient 4 had typical
all-day orthostatic headache that spontaneously transformed into second-half-of-the-day headache. Head MRI
at the time of second-half-of-the-day headache showed
improvement in the changes of spontaneous intracranial
hypotension compared to an earlier head MRI during typical all-day orthostatic headache, with near complete resolution of diffuse pachymeningeal enhancement.
Patients 1, 2, and 3 described second-half-of-the-day
headache as a residual symptom after receiving varying
numbers of epidural blood patches for typical all-day
orthostatic headache. When reimaged in the setting of
second-half-of-the-day headache, head MRI showed

improvement in the changes of spontaneous intracranial

hypotension in patients 1 and 2 (Fig. 1). Patient 1 underwent spine MRI in the setting of second-half-of-the-day
headache as well. This was also improved (an extradural
CSF collection extending from T2 to T9 had decreased in
size compared to earlier imaging during typical all-day
orthostatic headache). In patient 3, head MRI during second-half-of-the-day-headache demonstrated persistent
pachymeningeal thickening and enhancement with mildly
increased cerebellar tonsillar herniation. Spine MRI in this
patient was unchanged, with persistent cervical pachymeningeal thickening and enhancement, a very thin extraaxial dorsal fluid collection extending from C2 to C3, and
prominent nerve root sleeve diverticuli at multiple levels.
This prompted additional testing, including an MR myelogram and positive pressure CT myelogram, both with
delayed images at 4 h. Although multiple definite CSF
leaks at the upper cervical and lower thoracic levels had
been visualized in this patient on MR and CT myelograms
during typical all-day orthostatic headache, repeat imaging
showed no definite CSF leaksthough several areas were
suspicious for slow-flow leaks. Opening pressure during

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J Neurol (2012) 259:306310

typical all-day orthostatic headache was 76 mmH2O. When

repeated during second-half-of-the-day headache, it was
higher at 170 mmH2O. This was the only patient who
underwent lumbar puncture with measurement of opening
pressure and myelography at the time of second-half-ofthe-day headache.
Follow-up information was available in four patients,
ranging from 8 days to 9.7 years (mean 4.5 years) subsequent to their initial evaluation at our institution. Due to
the mild or improving nature of their symptoms, patients 1
and 5 underwent no investigations beyond head and spine
MRI and received no treatment for their second-half-ofthe-day headache. Both spontaneously improved with
complete or near-complete resolution of symptoms over
time. Follow-up imaging in patient 5 confirmed that the
head MRI findings of intracranial hypotension had
resolved. In patient 2, residual second-half-of-the-day
headache after epidural blood patch eventually progressed
into all-day orthostatic headache again. She continued to
receive periodic epidural blood patches and fibrin glue
injections with at most transient relief over the next 3 years
until eventually undergoing surgical repair of leaks elsewhere. This provided 5 months of complete symptom relief
followed by recurrent orthostatic headache. A second surgery provided only partial relief, and she continued to
require periodic epidural blood patches and fibrin glue
injections with residual and recurrent second-half-of-theday headache over the next year. She then returned to our
institution and received a high-volume lumbar epidural
blood patch that provided complete symptom relief for
several months until a coughing fit resulted in recurrent
second-half-of-the-day headacheagain successfully treated with a high-volume lumbar epidural blood patch.
Patient 3 underwent multi-level high-volume epidural
blood patchesfirst at the upper and lower thoracic levels
and then at the lower thoracic and lumbar levelswith
only transient relief of his second-half-of-the-day, Valsalva, and exertional headaches. He was advised to return
for a repeat evaluation in 6 months if symptoms persisted.

Discussion
Occurrence or aggravation of a variety of headache types in
the afternoon is not uncommon. However, in the setting of
CSF leak, second-half-of-the-day-headache usually maintains orthostatic features andin the setting of MRI
changes due to intracranial hypotensionlikely indicates
ongoing CSF leak.
The timing of second-half-of-the-day headache in the
clinical course of patients with CSF leak (i.e., an initial
symptom of CSF leak, a lingering symptom as CSF leak is
spontaneously resolving, or a residual or recurrent

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symptom after epidural blood patch or surgical repair)

suggests that it is a manifestation of a slow-flow CSF leak
or a leak that has been slowed due to previous treatments.
The MRI findings in patients with second-half-of-the-day
headache provide further support to this theory, as the
changes of intracranial hypotension on head and spine MRI
were frequently improved during second-half-of-the-day
headache compared to MRI during typical all-day orthostatic headache.
At our institution, we do not routinely monitor CSF
opening pressure throughout the clinical course of patients
with CSF leak, especially in the face of mild or improving
symptoms. Patients with CSF leak are also understandably
reluctant to undergo invasive tests involving dural puncture. Thus, not all patients in our study underwent lumbar
puncture at the time of second-half-of-the-day headache. In
the one patient in whom it was measured, CSF opening
pressure was higher during the second-half-of-the-day
headache than during the typical all-day orthostatic headache. This would also support our theory that second-halfof-the-day headache is a manifestation of slow-flow CSF
leak.
One patient in our series underwent MR and positive
pressure CT myelography at the time of second-half-ofthe-day-headache, both showing several areas suspicious
for slow-flow CSF leak. This was in contrast to myelography during typical all-day orthostatic headache, when
multiple areas of definite CSF leak were visualized. While
myelography is an accurate test for identifying the site of
spinal CSF leaks, very slow flow leaks may evade detection
even on delayed images [13].
The 2004 International Classification of Headache Disorders, 2nd edition defines headache related to spontaneous
intracranial hypotension as a one that worsens within
15 min of sitting or standing [14]. In one study of 90
patients with spontaneous intracranial hypotension confirmed by gadolinium-enhanced head MRI, 59% met this
criterion [6]. Another 16% described headache onset within
2 h of sitting or standing. Our data demonstrate that the
time to headache onset or worsening can be even longer in
the case of second-half-of-the-day headache. This delay
likely represents the time it takes for enough CSF volume
to be depleted through a slow-flow leak to cause CSF
hypovolemia and associated headache. In most patients, the
resulting headache is intense enough that they are prompted to lie down and thus recognize the orthostatic features
of their symptoms. Many patients in this series would
intentionally do so in anticipation of an evening engagement so as to avoid ongoing headachepresumably by
replacing some of the depleted CSF volume.
Limitations of this study include its retrospective design,
relying on data collected and recorded in a clinical setting.
Thus, the diagnostic evaluation in each patient was guided

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by the clinical context. However, all patients were seen by

a single examiner (B.M.), which brings some degree of
consistency to the clinical evaluation and documentation.
Another limitation is that of referral bias, as patients with
mild or improving symptoms are less likely to be seen at a
tertiary referral center, while unusual presentations are
more likely to be encountered.
In conclusion, afternoon-only or afternoon-predominant
headache in the general population is seen in a variety of
headache types. However, in the setting of spontaneous
CSF leak, second-half-of-the-day headache frequently has
orthostatic features and is likely a manifestation of ongoing
slow-flow leak. Association of second-half-of-the-day
headache with CSF leak in the patients reported here is
supported by persistent changes of intracranial hypotension
on head MRI. Furthermore, in addition to prominent
orthostatic features and characteristic MRI changes, the
patients frequently had other symptoms commonly associated with CSF leak (e.g., dizziness, tinnitus, ear fullness,
or muffled hearing, nausea (especially if orthostatic), neck
stiffness or discomfort, and horizontal diplopia) [6, 15].
Conflict of interest

None.

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