Second-half-of-the-day headache as a manifestation of spontaneous CSF leak
- First Online:
- Cite this article as:
- Leep Hunderfund, A.N. & Mokri, B. J Neurol (2012) 259: 306. doi:10.1007/s00415-011-6181-z
- 173 Views
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.
KeywordsHeadacheIntracranial hypotensionCerebrospinal fluid leakOrthostatic headacheLow pressure syndrome
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 , thunderclap headache at onset before orthostatic features become apparent , non-orthostatic chronic daily headache , orthostatic “coat hanger” neck and shoulder discomfort with or without occipital headache , or rarely paradoxical postural headache (present in recumbency, relieved in the upright position) . While most patients with spontaneous intracranial hypotension experience headache within 2 h of sitting or standing , 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 . The objective of this study is to draw attention to this phenomenon, describe the clinical features of such patients, and propose possible pathophysiologic mechanisms.
Those patients evaluated by one of us (B.M.) between January 1, 2000 and December 31, 2009 for spontaneous 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.
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 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.
Clinical characteristics of patients with second-half-of-the-day headache
Type of second-half-of-the-day headache
Timing in clinical course
Residual symptom after three epidural blood patches for all-day orthostatic headache
Tinnitus and altered hearing
Residual symptom after epidural blood patch for all-day orthostatic headache; residual/recurrent symptom after a second surgical repair and multiple epidural blood patches
Neck and upper back tightness/pain
Residual symptom after epidural blood patch for all-day orthostatic headache, exertional, and Valsalva headache
All-day orthostatic headache that over time spontaneously evolved into second-half-of-the-day headache
Initial symptom, evolved into all-day orthostatic headache within a few days
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 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-the-day 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.
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-of-the-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-the-day 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 headache—again successfully treated with a high-volume lumbar epidural blood patch. Patient 3 underwent multi-level high-volume epidural blood patches—first at the upper and lower thoracic levels and then at the lower thoracic and lumbar levels—with 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.
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 and—in the setting of MRI changes due to intracranial hypotension—likely 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 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-half-of-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-of-the-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 .
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 . In one study of 90 patients with spontaneous intracranial hypotension confirmed by gadolinium-enhanced head MRI, 59% met this criterion . 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 headache—presumably 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 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