Review Article Address correspondence to Dr Bahram Mokri, Mayo Clinic Neurology Department, E8A, 200 First Street SW, Rochester, MN, 55905, [email protected]. Relationship Disclosure: Dr Mokri reports no disclosure. Unlabeled Use of Products/Investigational Use Disclosure: Dr Mokri discusses the off-label use of gadolinium as an intrathecal agent. * 2015, American Academy of Neurology.

Spontaneous Intracranial Hypotension Bahram Mokri, MD, FAAN ABSTRACT Purpose of Review: Spontaneous intracranial hypotension results from CSF volume depletion, nearly always from spontaneous CSF leaks. Spontaneous intracranial hypotension is increasingly diagnosed in practice; the number of atypical, unconfirmed, and doubtful cases is also increasing, as are treatment failures. These confront neurologists and create many challenges. This review provides neurologists with a guide to diagnosis, evaluation, and treatment of spontaneous intracranial hypotension. Recent Findings: The clinical spectrum of spontaneous intracranial hypotension is expanding. Spontaneous CSF leak is considered a disorder with a variety of clinical manifestations and imaging features, sometimes quite different from what may be seen after dural puncture. The anatomy of the spontaneous CSF leak is frequently complex, with contributions from disorders of the connective tissue matrix and associated preexisting areas of dural weakness and meningeal diverticula. To locate the site of the leak, CT myelography is still the study of choice. For rapid-flow leaks, dynamic CT myelography has been very helpful, while slow-flow leaks can remain a lingering challenge. The fundamental question of whether a CSF leak is present in uncertain cases can be best answered by radioisotope cisternography. In most cases, epidural blood patch is the main treatment; however, bilevel or multilevel epidural injections are gaining some momentum as treatment for selected cases. Summary: This article outlines various clinical aspects of spontaneous intracranial hypotension, including headache characteristics, CSF changes, and imaging findings and their underlying mechanisms, as well as treatments and disease complications. Continuum (Minneap Minn) 2015;21(4):1086–1108.

INTRODUCTION Intracranial hypotension typically results from a CSF leak, which, in turn, leads to a decrease in CSF volume. The old theories of CSF overabsorption or underproduction have never been substantiated. Decrease in CSF volume rather than decrease in CSF pressure is the core pathogenetic factor (independent variable), while CSF pressures and clinical and imaging changes are variables dependent on CSF volume. CSF opening pressure is normal in a substantial minority of patients; therefore, terms such as CSF hypovolemia, CSF volume depletion, and CSF leak have appeared in the literature and are used interchangeably with spontaneous intracranial hypotension.

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Several conditions can cause loss of CSF volume. Spontaneous CSF leak is the most challenging cause and the main theme of this review. Because of the enormous impact of MRI, the diagnosis is made much more commonly, leading to the recognition of a substantially broader clinical spectrum of this disorder. Spontaneous CSF leak should not be equated with postdural puncture headaches, as substantial differences often exist in the overall clinical presentation, anatomy of the leak, response to treatment, and clinical outcome. Essentially, all cases of spontaneous intracranial hypotension result from spontaneous CSF leaks, typically at the level of the spine. Spontaneous (nontraumatic) leaks from the skull base (eg,

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cribriform plate) occur only rarely. When patients with spontaneous intracranial hypotension report nasal drainage of clear fluids, in the overwhelming majority (although not always) it turns out not to be CSF. CSF DYNAMICS The choroid plexus secretes more than 75% of the CSF; the rest is secreted by the brain capillaries entering the ventricles via the ependyma. The rate of CSF formation, in contrast to its volume, is fairly constant (in adults 0.35 mL per minute or about 500 mL per 24 hours). CSF is absorbed by arachnoid villi into the cerebral venous sinuses and veins via a valvelike mechanism called bulk flow.1 A minor portion of the CSF is absorbed into the cerebral vessels by simple diffusion, and another small portion is likely absorbed via the lymphatics of the cribriform plate region to the nasal submucosa.2 Old autopsy data estimated the total volume of CSF at about 150 mL. MRI volumetric studies point to larger volumes (approximately 200 mL or more in adults age 24 to 80, with substantial variability). This is not a surprise to the neurologist, as marked variation in the size of the ventricles and subarachnoid spaces on head MRI are seen in everyday practice, particularly in the young versus the elderly. At the spinal level, CSF volume is smaller in obese individuals. In the horizontal position, CSF pressures at lumbar, cisternal, and presumably intracranial or vertex levels are equal, measuring about 65 mm to 195 mm of water. In the vertical position, these pressures diverge. The vertex pressure becomes negative, while lumbar pressure increases. The relationship between CSF pressure and volume is exponential. Withdrawal of approximately 10% of CSF will decrease the already negative vertex pressure in the upright position by more than 40%.1,3 Continuum (Minneap Minn) 2015;21(4):1086–1108

ETIOLOGY The causes of intracranial hypotension are listed in Table 10-1.4 Regarding etiology, it is the spontaneous group that presents the real challenge. Its exact cause often remains unclear. Preexisting dural weakness (indicated by meningeal diverticula, dilated nerve root sleeves, or other evidence as listed in Table 10-1), likely related to a heritable disorder of the connective tissue matrix, has gained momentum as a significant contributory factor. In the setting of preexisting dural weakness, an otherwise trivial trauma may be an etiologic factor in some patients (Case 10-1; Figure 10-1). CLINICAL MANIFESTATIONS Headache The most common clinical manifestation of spontaneous intracranial hypotension is orthostatic headache, a headache occurring while the patient is in an upright position that is relieved in recumbency.4,15Y17 The interval from becoming upright to the appearance of headache or relief from it with recumbency is classically assumed to be a few minutes; in reality, considerable variability exists, and in many patients it is longer. The headache may be throbbing, but often it is described as a pressure sensation that can range from dull to very severe. It is often, but not always, bilateral, and the location is highly variable: frontal, fronto-occipital, holocephalic, or occipital. Two points need emphasizing: not all patients with orthostatic headache have CSF leaks (although the majority do), and not all headaches related to CSF leaks are orthostatic. The variability is substantial (Table 10-2). Sometimes with chronicity, the orthostatic features may attenuate with gradual transformation into a lingering chronic and daily headache.

KEY POINTS

h Spontaneous intracranial hypotension nearly always results from spontaneous CSF leaks at the spinal level. Spontaneous leaks from the skull base (eg, cribriform plate) occur only rarely.

h The relationship between CSF volume and pressure is exponential. Withdrawal of about 10% of CSF volume will decrease the already negative vertex CSF pressure (in the upright position) by more than 40%.

h Many patients with spontaneous CSF leaks have meningeal diverticula or display stigmata of heritable disorders of the connective tissue matrix (preexisting dural weakness). Some report a preceding, often trivial, trauma.

h Not all orthostatic headaches are due to CSF leaks, and not all headaches in those with CSF leaks are orthostatic. With chronicity, the orthostatic features of headaches may diminish.

Manifestations Other Than Headaches The clinical manifestations of spontaneous intracranial hypotension (CSF hypovolemia, spontaneous CSF leak) apart www.ContinuumJournal.com

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Intracranial Hypotension KEY POINT

h Spontaneous CSF leaks should not be equated with postdural puncture headaches, but as a disorder with a broad spectrum of clinical presentations. The anatomy of the leak in spontaneous intracranial hypotension and its response to treatment are often different than in postdural puncture headaches.

a TABLE 10-1 Etiology of CSF Hypovolemia or CSF Leaks

b True hypovolemic state, when total body water (including CSF) is reduced b Overdraining CSF shunts b Traumatic CSF leaks Obvious major injuries (eg, from motor vehicle accidents, sports injuries) Brachial plexus injuries (eg, nerve root sleeve tears, avulsions)5 Iatrogenic (eg, following dural punctures or epidural catheterizations) Postsurgical (eg, after cranial, spinal, sinus, or ear surgeries) b Spontaneous CSF leaks (major etiologic challenge) Unknown cause Preexisting dural sac weakness, supported by one or more of the following: Presence of meningeal diverticula, often, but not always, multiple6,7 Ectasia of dural sac8 Surgical anatomical observations of attenuated to near-absent dural zones9 Clinical stigmata of disorders of the connective tissue matrix10 Marfan syndrome or marfanoid features Joint hypermobility Retinal detachment at young age Abnormalities of elastin/fibrillin in dermal fibroblast cultures11 Familial occurrence of the leaks12 Personal or family history of arterial dissections, aneurysms or nonrheumatic valvular heart disease such as bicuspid aortic valve10,12 Trivial trauma (perhaps becoming relevant in the setting of a preexisting dural weakness) b Herniated discs or spondylotic spurs piercing or weakening the dura13,14 CSF = cerebrospinal fluid. a Modified with permission from Mokri B, Neurol Clin.15 B 2014 Elsevier Inc. www.sciencedirect. com/science/article/pii/S0733861913001163.

from headaches are listed in Table 10-3. Of these, neck and interscapular pain, cochleovestibular manifestations, and perhaps nausea are far more common than others. If present, the level of the spinal pain may not necessarily correspond to the level of the leak and, indeed, often does not. The variability in headache characteristics and long list of associated symptoms emphasize the broad clinical spectrum of this disorder and illustrate the fact that spontaneous CSF leaks should no longer

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be equated with postdural puncture headaches. Rather, spontaneous CSF leak is a disorder with a variety of clinical manifestations, in which the anatomy of the leak as well as the response to treatment and outcome are often different from postdural puncture headaches. Mechanisms of Clinical Manifestations One consequence of a decrease in CSF volume is sinking of the brain. This leads

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Case 10-1 A 23-year-old woman developed orthostatic headaches and pain in the posterior neck and shoulder muscles bilaterally in a coat hanger distribution. She had joint hypermobility (Figure 10-1A) with a strong family history of the same, a family history of CSF leaks (two sisters), and a strong family history of aortic aneurysms and dissection.12,15 Treatments for tension headaches were ineffective. Head MRI showed descent of cerebellar tonsils (Figure 10-1B), enlarged pituitary gland, flattened optic chiasm, and obliteration of the perichiasmatic cistern but no abnormal pachymeningeal enhancement (Figure 10-1C). Spine MRI showed extra-arachnoid fluid (Figure 10-1D) that extended across several spinal segments. Dynamic CT myelography showed a leaking meningeal diverticulum at T11-T12 (Figure 10-1E). This leaking diverticulum was surgically removed, and the small orifice of its connection to the dura was sutured. The patient’s headaches resolved, and further imaging was not needed.

Images of the patient in Case 10-1. A, Joint hypermobility. B, Sagittal head MRI showing descent of the cerebellar tonsils, flattened anterior pons, obliteration of prepontine cistern, and crowded posterior fossa. C, Gadolinium-enhanced coronal MRI transecting the sella. Note the enlarged pituitary and obliteration of perichiasmatic cistern, with little abnormal pachymeningeal enhancement. D, Heavily T2-weighted axial spinal MRI showing a meningeal diverticulum. E, Axial hyperdynamic CT myelography showing this to be a leaking meningeal diverticulum (arrow).

FIGURE 10-1

Reprinted with permission from Mokri B, Neurol Clin.15 B 2014 Elsevier Inc. www.sciencedirect.com/science/article/pii/S0733861913001163.

Comment. This case illustrates several points regarding diagnosis of CSF leaks: 1. It is not uncommon for patients with CSF leaks to be initially treated for tension-type headache, migraine, or ‘‘sinus’’ headaches before the correct diagnosis is established. 2. Absence of abnormal pachymeningeal enhancement in active CSF leaks is uncommon but not rare. Fortunately, other imaging abnormalities often help support the diagnosis. 3. Clinical and historical clues to a heritable disorder of the connective tissue matrix can be detected in a significant minority of patients with spontaneous CSF leaks. These likely promote formation of meningeal diverticula and the preexisting areas of dural attenuation so frequently seen in these patients through imaging studies and surgical anatomical observations.9 Continuum (Minneap Minn) 2015;21(4):1086–1108

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Hypotension (CSF Leak, TABLE 10-2 Headache in Intracranial CSF Hypovolemia)a b Orthostatic headaches (present in upright position and relieved in recumbency) b Neck or interscapular pain or a lingering nonorthostatic headache preceding the orthostatic headache (by days or weeks) b Orthostatic headache gradually evolving into lingering nonorthostatic chronic and persistent headache (transformed orthostatic headaches) b Nonorthostatic daily headaches from the start b Exertional (and Valsalva-induced) headaches18 b Acute thunderclaplike onset of orthostatic headaches19 b Second-half-of-the-day headaches (often with some orthostatic features)20 b Paradoxical orthostatic headaches (present in recumbency, relieved when upright)21 b Intermittent headaches associated with intermittent leaks b No headaches at all, the ‘‘acephalgic form’’ (patients present with other clinical manifestations of the CSF leak) CSF = cerebrospinal fluid. a Modified with permission from Mokri B, Neurol Clin.15 B 2014 Elsevier Inc. www.sciencedirect.com/ science/article/pii/S0733861913001163.

to traction or distortion of the anchoring or supporting pain-sensitive structures of the brain and therefore to headaches that are orthostatic or have some orthostatic features.1,26 Dilatation of intracranial venous structures likely also plays a role (Case 10-2; Figure 10-2). Traction, distortion, or compression of some of the cranial nerves, the lobes of the brain, brainstem, mesencephalon, and diencephalon are thought to be responsible for the nonheadache manifestations of this disorder (Table 10-4).1 Cochleovestibular manifestations (eg, tinnitus, hearing change, dizziness) may be related to traction on the eighth cranial nerve, but an alternative and more plausible mechanism is altered pressure in the perilymphatic/endolymphatic fluid of the inner ear.22 DIAGNOSIS Several diagnostic tools and methods have been implemented in patients with spontaneous intracranial hypotension.

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CSF Examination CSF findings may show considerable variability (Table 10-5). Radioisotope Cisternography Indium-111 is the radioisotope of choice when conducting radioisotope cisternography. It is introduced intrathecally via a lumbar puncture, and its dynamic flow is followed by sequential scanning (Figure 10-3, upper panel) done at predetermined intervals up to 24 or even 48 hours. Normally by 24 hours, but often even earlier, abundant radioactivity is detected over the cerebral convexities (Figure 10-3, middle and lower panels).29 In CSF leaks, several changes and mimics may be encountered (Figure 10-4A). Paucity of activity over the cerebral convexities at 24 hours (Figure 10-4C) is the most common cisternographic abnormality in CSF leaks. Paradural activity pointing to the level or approximate site of the leak (Figure 10-4B) is less common. Activity within meningeal diverticula or

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TABLE 10-3 Nonheadache Manifestations of Spontaneous CSF Leaks Manifestations

Comments

Spine pain

Neck and/or interscapular pain (common), low back pain (much less common); do not expect the site of the pain to necessarily correspond to the site of the leak

Cochleovestibular manifestations

Tinnitus, nonpulsatile Change in hearing (eg, muffled, distant, echoed, distorted, decreased) Dizziness (eg, vertigo, lightheaded feeling, wooziness); rarely Me´nie`relike presentation22

Nausea/emesis

Nausea, often orthostatic Emesis is much less common, typically orthostatic

Diplopia/visual symptoms

Unilateral or bilateral sixth cranial nerve palsy more often than third, fourth, or multiple cranial nerve palsies; visual blurring, field defects23

Cognitive/behavioral changes

Memory difficulties Personality change, less organized, cannot get things done or complete projects, less tidy, inappropriate behavior, frontotemporal dementiaYlike presentation24

Gait unsteadiness

Regardless of presence or absence of abnormal head sensation

Movement disorders

Chorea, parkinsonism, tremor25

Uncommon or rare manifestations4,15

Numbness/paresthesia in face, posterior head, upper limbs Radicular upper extremity manifestations Encephalopathy, stupor, coma Trouble with sphincter control Galactorrhea Visual field cut Bibrachial amyotrophy

CSF = cerebrospinal fluid.

dilated nerve root sleeves when large enough (Figure 10-4F), ‘‘backwash phenomenon’’ (extradural egress of isotope from the injection site) (Figure 10-4-E), or inadvertent injection of a portion of radioisotope extradurally may appear as collections of paradural activity (Figure 10-4D). CT myelography is often helpful in differentiating these mimics from true CSF leaks. Early appearance of radioactivity in the kidneys and the urinary bladder is another fairly common finding, indicating that intrathecally introduced radioisotope has been extravasated, entered the Continuum (Minneap Minn) 2015;21(4):1086–1108

systemic circulation, cleared via the kidneys, and appeared early in the urinary bladder. However, this is not always a very reliable indicator of CSF leak as inadvertent extradural injection or backwash of the radioisotope through the dural puncture site may also lead to early appearance of radioactivity in the urinary bladder. Occasionally, digital subtraction myelography in patients with spontaneous intracranial hypotension has demonstrated direct CSF venous fistulas, which can also be a factor in early appearance of bladder activity. Rare observations

KEY POINT

h On radioisotope cisternography, early activity in the urinary bladder can be seen in CSF leaks but also in the backwash phenomenon and in inadvertent partial epidural injection of radioisotope.

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Case 10-2 A 44-year-old man presented with increasing orthostatic headaches, dizziness, nausea and occasional emesis, and bowel and bladder incontinence. Ten years earlier, he had undergone surgery for a presumed Chiari type 1 malformation for similar symptoms without the benefit of a contrast-enhanced MRI. There was an initial decrease in symptoms, but they lingered and later increased. There were no neurologic deficits. Head MRI at the time of the current evaluation (Figure 10-2A) showed diffuse pachymeningeal enhancement, enlarged pituitary, and flattening of the optic chiasm in addition to descent of the cerebellar tonsils and postoperative changes from the previous suboccipital craniectomy and C1 laminectomy. CSF opening pressure was 60 mm of water with normal CSF analysis except for a mild increase in protein concentration. CT myelography showed a fairly large meningeal diverticulum in the left L2 neural foramen (Figure 10-2B and 10-2C). This was surgically repaired. Two months after surgery, there was complete resolution of the symptoms and the MRI abnormalities (Figure 10-2D). He reported vague visual symptoms intermittently, beginning 1 week postoperatively. There was bilateral papilledema (Figure 10-2E and 10-2F). The rebound intracranial hypertension responded well to acetazolamide.27

Images of the patient in Case 10-2. At presentation with orthostatic headaches, enhanced T1-weighted coronal head MRI transecting the sella (A) showing diffuse pachymeningeal enhancement (red arrows), enlargement of the pituitary (blue arrow), and flattened optic chiasm. CT myelography (B, C, green arrows) identifying leaking meningeal diverticulum. Surgical repair was followed by resolution of the orthostatic headache and reversal of the head MRI abnormalities, including decrease in size of the enlarged pituitary (D, arrow). Note mildly smaller size of the ventricles in panel A compared with panel D, pointing to presence of ‘‘ventricular collapse’’ in panel A, which is often subtle and recognized retrospectively; sometimes, however, it is quite obvious. Left (E) and right (F) optic fundus photos showing bilateral papilledema including hemorrhage in the left eye.

FIGURE 10-2

27

Reprinted with permission from Mokri B, Mayo Clin Proc. B 2002 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. www.mayoclinicproceedings.org/article/S0025-6196(11)61815-6/fulltext.

Continued on page 1093

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Continued from page 1092 Comment. In addition to illustrating orthostatic headaches and several other clinical features, plus demonstrating several MRI abnormalities seen in CSF leaks, this case shows the following: 1. Sinking of the brain may mimic Chiari type 1 malformation, and obtaining an enhanced head MRI in this situation is essential. 2. Clinical and MRI abnormalities resolve if the leak is completely stopped. 3. A period of rebound intracranial hypertension sometimes may follow successful treatment of CSF leaks.

have been reported on CSF fistulas between a nerve root sleeve and a lymphatic malformation as the cause of intracranial hypotension.30Y32 Considering the increasing number of patients with atypical features and an uncertain or doubtful diagnosis, the fundamental question to be addressed first is if a CSF leak is actually present before subjecting TABLE 10-4

the patient to more involved, more invasive, and more costly measures. In this regard, radioisotope cisternography is most helpful, as the absence of radioactivity over the cerebral convexities at 24 hours strongly suggests an active CSF leak, while its presence makes the diagnosis very unlikely. In evaluating patients with suspected CSF leaks, radioisotope

Proposed/Presumed Mechanisms of Clinical Manifestations of Spontaneous Intracranial Hypotension/Spontaneous CSF Leaks

Clinical Manifestation

Mechanism

Headaches

Sinking of brain, causing stretch and distortion of pain-sensitive suspending structures Engorgement of cerebral venous sinuses and veins

Cochleovestibular manifestations (eg, hearing change, tinnitus, dizziness)

Stretching of eighth cranial nerve

Cranial nerve palsies

Stretching or compression of the related cranial nerves

Visual blurring, field cuts

Compression or vascular congestion of the intracranial part of the optic nerves

Upper limb symptoms

Stretching of the cervical nerve roots or irritation of the nerve roots by dilated epidural venous plexus

Encephalopathy, stupor, coma

Diencephalic compression

Memory difficulty, personality change, frontotemporal dementiaYlike presentation

Descent and distortion of brainstem and diencephalon, compression of frontal and temporal lobes

Cerebellar ataxia, parkinsonism, bulbar manifestations

Compression of the posterior fossa and deep brain structures

Gait disorder

Spinal cord venous congestion, cord distortion, or resultant deformity

Galactorrhea, increased prolactin

Distortion of pituitary stalk

Chorea

Pressure on basal ganglia or their connections

Pressure changes in perilymphatic/endolymphatic fluids of inner ears (a more plausible theory)

CSF = cerebrospinal fluid.

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a TABLE 10-5 CSF Findings in Spontaneous CSF Leaks

Feature

Finding

Opening pressure

Often low, occasionally atmospheric, or rarely even negative. Sometimes within normal limits even on repeated taps despite active CSF leak.1,28 Sometimes variable CSF opening pressures may be recorded on different occasions in the same patient. This may be related to variability in rate of flow of the leak.

Color

Often clear, occasionally xanthochromic, sometimes blood tinged. Note that difficult and traumatic taps are not unusual when CSF opening pressure is very low. Engorgement of the epidural venous plexus is also a contributory factor.

Protein concentration

May be normal or high. Values up to 100 mg/dL are not uncommon and protein concentrations as high as 1000 mg/dL have been rarely observed.4

Leukocyte count

May be normal, but a lymphocytic pleocytosis of up to 50 cells/mm3 is not uncommon and higher counts are not rare. Counts as high as 222 cells/mm3 have been documented.1,4

Erythrocyte count

May be normal or elevated (sometimes considerably, in connection with traumatic taps).

Cytology and microbiology

Normal/negative.

Glucose concentration

Never low.

CSF = cerebrospinal fluid. a Modified with permission from Mokri B, Neurol Clin.15 B 2014 Elsevier Inc. www.sciencedirect.com/science/article/pii/S0733861913001163.

KEY POINTS

h Absence of activity over the cerebral convexities at 24 hours is the most common and reliable radioisotope cisternographic finding in CSF leaks. Paradural activity identifying the site of the leak is less common, and mimics may need to be excluded.

h A comprehensive head MRI study for CSF leaks should include T1-weighted sagittal midline and gadolinium-enhanced T1-weighted coronal images through the sella and pituitary.

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cisternography is not a substitute or competitor for other imaging techniques, but rather has its own particular indications. Head CT The usual head CT is of limited value in evaluation of spontaneous CSF leaks. MRI of Head and Spine Abnormalities due to CSF leaks that may be seen on MRI of the head are listed in Table 10-6 and shown in Figure 10-1B and 10-1C, Figure 10-2A and 10-2D, Figure 10-5, Figure 10-6, and Figure 10-7. Detailed references can be found in references 4 and 15. Major head MRI abnormalities include diffuse pachymeningeal gadolinium enhancement without abnormal leptomeningeal enhancement, sinking or sagging of the brain, descent of the brainstem, subdural fluid collections, enlarged pituitary, engorged cerebral venous sinuses, and decrease in size of the ventricles. A complete head MRI for

evaluation of spontaneous CSF leaks should include T1-weighted midline sagittal views as well as gadoliniumenhanced T1-weighted coronal views through the sella and pituitary. The former will clearly show imaging abnormalities of sinking of the brain, and the latter will show such abnormalities as diffuse pachymeningeal enhancement, enlarged pituitary, and flattening of the optic chiasm. Although diffuse pachymeningeal enhancement is the most prominent head MRI abnormality in spontaneous CSF leaks, in some patients it is absent. Furthermore, in head MRIs obtained by 3Tesla machines, the pachymeninges may appear more prominent and may erroneously be interpreted as abnormal. Abnormalities due to CSF leaks that may be seen on MRI of the spine are listed in Table 10-7 and shown in Figure 10-8 and Figure 10-9. Detailed references can be found in references 4 and 15. As detailed in Table 10-7, major spine MRI abnormalities in spontaneous CSF leaks

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KEY POINTS

h Beware that with 3-Tesla machines, the meninges normally appear somewhat thicker and more prominent.

h Some patients with CSF leaks may not show pachymeningeal enhancement on MRI.

h With CSF volume loss, a compensatory intracranial venous hyperemia occurs, resulting in meningeal hyperemia-pachymeningeal enhancement and pituitary and cerebral venous sinus engorgement.

Radioisotope cisternography. Schematic demonstration of principles of radioisotope cisternography (upper panel). Radioisotope is introduced intrathecally via lumbar puncture (A), gradually expands in cephalad direction (B), and reaches basal cisterns (C), sylvian and interhemispheric fissures (D), and, in normal circumstances, cerebral convexities and vertex (E) usually by 24 hours and often earlier. Posteroanterior view (middle panel) and lateral view (lower panel) of normal radioisotope cisternographic images. The images are taken at predetermined intervals. Note cephalad expansion of radioisotope from lumbar region well reaching the cerebral convexities and vertex by 24 hours.

FIGURE 10-3

PA = posteroanterior 29

Reprinted with permission from Mokri B, Headache. B 2014 American Headache Society. onlinelibrary.wiley.com/doi/10.1111/head.12421/abstract.

include subdural fluid collections, extradural extravasation of CSF, spinal dural enhancement, meningeal diverticula and dilated nerve root sleeves, and engorgement of epidural venous plexus. Mechanisms of MRI abnormalities. Recall the principles of the Monro-Kellie doctrine: ‘‘With intact skull, the sum of Continuum (Minneap Minn) 2015;21(4):1086–1108

volumes of brain plus CSF plus intracranial blood is constant.’’ Therefore, increase (or decrease) in one volume will result in decrease (or increase) in one or both of the remaining two. In CSF leak with CSF volume loss, given that the brain is nonexpandable and the rigid skull is noncollapsible, the decrease www.ContinuumJournal.com

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Radioisotope cisternography. A, Schematic demonstration of various findings after lumbar intrathecal introduction of radioisotope. Panels BYF show actual cisternographic images of what has been depicted schematically in panel A. B, Paradural activity, direct radioisotope cisternographic evidence of leak, more desirable diagnostically but encountered substantially less frequently than paucity of activity over the cerebral convexities at 24 hours, as seen in panel C. This is an indirect but very reliable evidence of CSF leak. D, Inadvertent mostly extradural injection. Note limited activity in the dural sac but activity in paraspinal soft tissues and intense activity in the kidneys and bladder. E, Backwash phenomenon related to egress of some of the radioisotope from the puncture site. Note fuzzy extradural activity in the lumbar region. The activity normally reaches cerebral convexities at 24 hours, and the fuzzy lumbar extradural activity diminishes and nearly clears within a few hours. F, Meningeal diverticula. These can be single, a few, or multiple. When single or just a few, beware that these are not necessarily taken as sites of CSF leakage.

FIGURE 10-4

Reprinted with permission from Mokri B, Headache.29 B 2014 American Headache Society. onlinelibrary.wiley.com/doi/10.1111/head.12421/abstract.

in CSF volume is compensated by an increase in intracranial blood volume, mainly the venous component.4,28,33 Therefore, intracranial venous hypervolemia occurs and may be reflected by dilatation of the cerebral venous sinuses,

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engorgement of the pituitary, and diffuse pachymeningeal engorgement. As the leptomeninges have blood-brain barriers and the pachymeninges do not, it is only the pachymeninges that enhance with gadolinium.1,15 Another volume

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TABLE 10-6 Head MRI Abnormalities in Spontaneous CSF Leaks Abnormality

Features and Comments

Diffuse pachymeningeal enhancement (Figure 10-2A red arrows)

May be thick, very thin, or anywhere in between, but it is uninterrupted, non-nodular, and involves both supratentorial and infratentorial pachymeninges. Note that when imaged with 3-Tesla magnet, pachymeninges normally appear more prominent.

No leptomeningeal enhancement

Leptomeninges have blood-brain barriers, while pachymeninges do not. Only pachymeninges enhance in this disorder. Leptomeningeal involvement would point to other or additional pathology.

Descent, ‘‘sinking,’’ or ‘‘sagging’’ of the brain (Figure 10-1B, Figure 10-5)

Descent of cerebellar tonsils, many mimic Chiari type 1 malformation. Descent of brainstem and mesencephalon, sometimes even without descent of cerebellar tonsils; here, itera lies below the incisural line.b Distortion of brainstem, mesencephalon, and diencephalon; flattening of anterior pons. Obliteration of some of the basal cisterns (eg, prepontine, perichiasmatic). Flattening of the optic chiasm. Crowding of posterior fossa.

Subdural fluid collections (Figure 10-6)

Often hygromas, bilateral, unilateral, or asymmetric; often over the cerebral convexities, often thin without compression of the underlying brain or flattening of underlying sulci. Sometimes subdural hematomas form that can become large, compress the underlying brain, and shift the midline.

Engorgement of pituitary (Figure 10-2A blue arrow, Figure 10-1C)

Pituitary enlargement, may mimic pituitary tumor or hyperplasia. At times, domed appearance on coronal images with flattened optic chiasm draped over it.

Engorgement of cerebral venous sinuses (Figure 10-7)

Enlargement and increased prominence of the venous structures.

Ventricular collapse (Figure10-2A contrasted with Figure 10-2D)

Decrease in size of ventricles.

a b

Iter: Cephalad opening of the aqueduct of Sylvius as seen in midsagittal views. Incisural line: Line drawn in midsagittal view between the anterior tubercular sellae and junction of the inferior sagittal sinus, straight sinus, and great vein of Galen.

compensatory mechanism is collection of subdural fluids. Similarly, spinal pachymeningeal enhancement and extra-arachnoid fluid collections can be seen on spine MRI. The spinal epidural space contains adipose and loose connective tissue plus the epidural venous plexus. With CSF hypovolemia, a relatively mild collapse of the Continuum (Minneap Minn) 2015;21(4):1086–1108

dural sac may lead to dilatation of the epidural venous plexus. Other consequences of CSF volume loss include a decrease in the size of the ventricles (‘‘ventricular collapse’’) and descent of the brain (descent of the cerebellar tonsils; crowding of the posterior fossa; decrease in size of some of the basal cisterns, such as the prepontine

KEY POINT

h Subdural fluid collections and dilatation of the epidural plexus are also volume compensatory phenomena in response to loss of CSF volume.

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FIGURE 10-5

A, Sagittal head MRI. Note descent of cerebellar tonsils below the foramen magnum. Iter (asterisk) is below the incisural line (dotted line). B, Lateral radioisotope cisternographic image. Note paucity of activity over the cerebral convexities at 24 hours.

or perichiasmatic cisterns; descent of the brainstem, at times accompanied by its deformity and increase in its anteroposterior diameter; and descent of iter [the cephalad opening of the aqueduct of Sylvius]). Myelography/CT Myelography Myelography and CT myelography may show several abnormalities: 1. Extra-arachnoid fluid that is focal or extending across several vertebral levels (in extreme cases, from cervical all the way to the lumbar level). 2. Meningeal diverticula (single or multiple, various sizes, different levels) may or may not be the site of CSF leakage even when large (Figure 10-2B and 10-2C). 3. Extradural egress of contrast extending into the paraspinal soft

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tissues. CT myelography is the most reliable test to show the exact site of leak (Figure 10-1E). It also provides an opportunity to measure the CSF opening pressure. The rate of CSF leak may range from very slow to very fast. The two extremes of rapid flow or slow flow present substantial challenges in locating the actual site of the leak. In rapid-flow leaks, the obstacle may be dealt with by proceeding with highspeed CT scanning of the spine immediately after the intrathecal injection of contrast, bypassing the myelographic portion of the study. This technique, known as dynamic CT myelography, and its variations have been very helpful in locating the site of the leakage in rapidflow leaks, as has digital subtraction myelography.34,35

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FIGURE 10-6

Coronal T2-weighted head MRI in a patient with CSF leak. Note bilateral subdural fluid collection isointense with CSF (hygromas). 15

Reprinted with permission from Mokri B, Neurol Clin. B 2014 Elsevier Inc. www.sciencedirect.com/science/article/pii/S0733861913001163.

FIGURE 10-7

Engorgement of cerebral venous sinuses in a patient with spontaneous CSF leak. The pachymeningeal enhancement is quite thin but is diffuse. 15

Reprinted with permission from Mokri B, Neurol Clin. B 2014 Elsevier Inc. www.sciencedirect.com/science/article/pii/S0733861913001163.

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TABLE 10-7 Spine MRI Abnormalities in Spontaneous CSF Leaks (CSF Hypovolemia) Abnormality

Features and Comments

Subdural/extra-arachnoid fluid collections (Figure 10-9)

May be focal or extend along several or many vertebral segments.

Extradural extravasation of CSF (Figure 10-1D, Figure 10-8C arrowheads)

Extends toward paraspinal soft tissues. May point to site or approximate site of CSF leak (unfortunately uncommonly). Highly T2-weighted images appear more ‘‘clean,’’ but are not a substitute to CT myelography in identifying the site of the leak.

Spinal dural enhancement (Figure 10-8A arrowheads)

At times, cervical spinal continuation of pachymeningeal enhancement is seen in head MRIs. It may be encountered at any spinal level but particularly the cervical.

Meningeal diverticula, dilated nerve root sleeves (Figure 10-8B)

May be single, multiple, small (few millimeters), or subcentimeter, but sometimes larger; not guaranteed to be the site of the leak.

Engorgement of epidural venous plexus (Figure 10-8D)

A volume compensatory response to partial spinal dural collapse as a consequence of decreased CSF volume. Can be cervical, thoracic, lumbar, or any combination.

MRI = magnetic resonance imaging; CSF = cerebrospinal fluid.

In slow-flow CSF leaks, several procedures have been tried, including: & Delayed CT scanning. & Intrathecal injection of fluid to elevate CSF pressure from low to normal levels before injection of contrast to increase the likelihood of CSF-contrast extravasation, which the author has referred to as positive pressure myelography. Results have been variable and not strong enough to generate significant enthusiasm. & Gadolinium myelography, which is essentially a spine MRI after intrathecal injection of gadolinium. This is sometimes helpful in detecting the site of a slow-flow CSF leak but not as much as initially hoped. This is an off-label use of gadolinium and should be considered only when the diagnosis of CSF leak is highly suspected and when the site of CSF leak has not been detected by other diagnostic techniques such as CT myelography.36 Locating the site of slow-flow CSF leaks frequently remains problematic

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and sometimes quite frustrating for both the patient and the physician. Considering the broad, and growing, clinical spectrum of spontaneous CSF leaks and substantial variability in many of its various aspects, a ‘‘what to do’’ algorithm is both important and complex, and will likely become even more complex in the future. Nonetheless, it can still prove useful (Figure 10-10).31 TREATMENT Table 10-8 lists the treatment modalities applied in spontaneous CSF leaks. Fortunately, with time, the leak stops spontaneously in some patients, and they become asymptomatic. Bed rest is traditionally recommended. Many patients, although not all, have enough orthostatic symptoms, at least initially, that they tend to stay recumbent much of the time anyway. Hydration is another traditionally recommended measure. This is often overhydration, as many patients are not dehydrated. A few studies have pointed to the efficacy of caffeine and theophylline, but clinically their use is often not impressive.37

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Spinal MRI abnormalities in spontaneous CSF leak. Note spinal pachymeningeal enhancement (A, arrowheads) seen on sagittal T1-weighted postcontrast head MRI; meningeal diverticula and dilated nerve root sleeves seen on gadolinium myelogram (B); epidural extravasation of fluid (C, arrowheads) on axial T2-weighted MRI; engorgement of epidural venous plexus (D) seen on sagittal T2-weighted MRI; and examples of elongated ventral extra-arachnoid fluid collections across several spinal levels (E, F) seen on axial T2-weighted MRIs.

FIGURE 10-8

4

Reprinted with permission from Mokri B, Headache. B 2013 American Headache Society. onlinelibrary.wiley.com/doi/10.1111/head.12149/full.

The efficacy of corticosteroids for control of the symptoms may range from none to fairly impressive (in a minority). Even when effective, this is often partial and of uncertain durability. Considering the potential side effects of extended corticosteroid therapy, this does not seem to be a long-term therapeutic solution.4,15 Use of vitamin A has recently been reported in anecdotal case reports, but the value of this approach requires further validation of efficacy, dose determination, and side effects. Intrathecal fluid infusions or epidural infusions of crystalloids or colloids Continuum (Minneap Minn) 2015;21(4):1086–1108

have been tried occasionally in a limited number of patients with limited remaining options and limited expectations.37Y39 Justified concerns exist about infection and catheter failure with prolonged infusions. Epidural blood patch is the treatment of choice in patients for whom an initial trial of simpler conservative managements fails.40,41 Because the diagnosis is often delayed, many patients have already exhausted the ‘‘time’’ and ‘‘bed rest’’ approaches. The effect of epidural blood patch is twofold: (1) an early effect (sometimes almost immediate) related simply to volume replacement and (2) a

KEY POINT

h The efficacy of corticosteroids for control of symptoms in spontaneous CSF leaks ranges from none to fairly impressive. Considering the side effects of their extended use and uncertain durability, they are hardly a long-term solution.

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FIGURE 10-9

Sagittal (A) and axial (B) T2-weighted spinal MRI demonstrating an elongated ventral extra-arachnoid fluid collection across several vertebral bodies (arrows).

latent effect resulting from sealing of the leak. In spontaneous leaks, the success rate with each epidural blood patch is approximately 30%.41 Many patients require more than one epidural blood patch. The success rate is significantly less impressive than that seen in postdural puncture headaches, where the first epidural blood patch gives relief in the vast majority and a second one in nearly all cases. This difference is a consequence of several factors, including the clarity of the level and site of the leak in postdural puncture leaks and the often more complex anatomy of the leak in spontaneous CSF leaks.

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Additional options include epidural injection of fibrin glue (translaminar or transforaminal), or a combination of fibrin glue and homologous blood.42,43 The epidural injections may be single level, bilevel, or even multilevel. They may be targeted, distant from the site of the leak, or ‘‘blind epidural blood patches’’ (when the site of CSF leak has not been determined). These blind patches of blood or blood plus fibrin glue are typically placed at the lumbar region.44 The volume of the homologous blood intended to be injected epidurally increased over time from 5 mL to 10 mL to 20 mL, for years considered by some as

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KEY POINT

h Before surgical intervention, it is essential to determine the exact site of the CSF leak. A meningeal diverticulum cannot be automatically assumed to be the site of the leak unless the leak has been demonstrated neuroradiologically.

FIGURE 10-10

An algorithm of what to do in cases of suspected spinal CSF leaks.

CSF = cerebrospinal fluid; MRI = magnetic resonance imaging; CE = contrast enhancement; EBP = epidural blood patch; RIC = radioisotope cisternographic imaging; CTM = CT myelography; DSM = digital subtraction myelography; GdM = gadolinium myelography.

a b

Study also provides opportunity to measure CSF opening pressure. Early extensive extra-arachnoid CSF egress may make detection of the exact site of the leak on CT myelography almost impossible.

the gold standard.40 Of course, this volume cannot be tolerated by all patients, while some patients have tolerated even higher volumes. Some physicians have practiced giving these higher volumes, especially for lumbar epidural blood patches, using the patient’s pain and intolerance as the stopping point. Overall, the tolerated volume for cervical and thoracic epidural blood patches seems lower than for lumbar epidural blood patches. For transforaminal CT-guided multilevel epidural blood patches, the intended volume is often about 3 mL.45 Approximately the same volume is used for transforaminal injection of fibrin glue, and 3 mL to 7 mL has been practiced for translaminar injections.46,47 These are approxContinuum (Minneap Minn) 2015;21(4):1086–1108

imate figures, with variations both a bit higher and lower used in practice. Overall, fibrin glue may not flow as freely as blood. Rare anaphylactic reactions to repeated epidural fibrin sealant injections have been reported.48 In selected cases, surgery may be effective; it is considered for those patients for whom conservative measures and lessinvasive treatments fail, such as epidural blood patches, or when the anatomy of the leak is such that success of nonsurgical approaches is predicted to be remote, such as when encountering a clearly leaking meningeal diverticulum that appears complex and relatively large.9,49 Surgery is not always straightforward, because the anatomy of the leak is not always simple.9 Sometimes the site of the www.ContinuumJournal.com

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a TABLE 10-8 Treatment of Spontaneous CSF Leaks

b Conservative measures Bed rest (typically patients with substantial orthostatic headaches tend to remain recumbent much of the time anyway) Coffee Hydration, or more accurately overhydration, as the large majority of patients are not dehydrated Time (might be the most important element) b Medications Analgesics (often, but not always, impractical as the effect of analgesics in the upright position may be only partial, and many patients become completely or substantially headache free in recumbency) Caffeine Corticosteroids Possibly vitamin A Theophylline b Abdominal binder b Epidural injections Fibrin glue and blood Fibrin glue (fibrin sealant) Homologous blood epidural blood patch: targeted, distant, bilevel, multilevel, ‘‘blind’’ (at lumbar level). May be translaminar, transforaminal, or CT-guided b Surgical repair of the leak b Other measures in special situations Epidural infusion of crystals and colloids Epidural saline infusions (uncertain, unpredictable efficacy or durability, risk of infection) Intrathecal fluid injection (for quick CSF volume replacement in rare instances of progressing obtundation, stupor, or coma from descent and compromise of brainstem and midbrain IV saline infusions CSF = cerebrospinal fluid; CT = computed tomography; IV = intravenous. a Reprinted with permission from Mokri B, Neurol Clin.15 B 2014 Elsevier Inc. www.sciencedirect.com/science/article/pii/S0733861913001163.

leak and the dural defect is in the anterior aspect of the dura, or the leak may be from a meningeal diverticulum or a defect or diverticulum of a nerve root sleeve. Each of these may have varying anatomical configurations and provide the surgeon with unpredicted challenges. It is essential, however, to try to locate the site of the CSF leakage before surgery and to realize that a meningeal diverticulum, even when

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large, may not necessarily be the actual site of the CSF leakage. With careful diagnostic evaluation and patient selection, surgical repair may yield positive outcomes. COMPLICATIONS OF CSF LEAKS Complications of CSF leaks are listed in Table 10-9 and include subdural hematomas, rebound intracranial hypertension

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TABLE 10-9 Complications of Spontaneous CSF Leaks Complication

Features and Comments

Subdural hematoma

May complicate subdural hygroma or be hematoma from start. Can range from thin and asymptomatic to large, compressing underlying brain and shifting the midline. Surgery may be needed if symptomatic or expanding.50 Creation of skull defect may increase sinking of brain.51 Vigilant postoperative care/follow-up important. Prudent to coordinate attempts to stop the leak. Nonurgent, small subdural hematomas may resolve with treatment of the leak (eg, epidural blood patch).

Rebound intracranial hypertension

Seen sometimes after successful treatment of CSF leaks. Often mild but occasionally more dramatic presentation including papilledema.27 Often self-limiting, but sometimes may take a frustratingly long course. Acetazolamide can help. Few patients have ended up with ventriculoperitoneal shunting.

Cerebral venous sinus thrombosis

Very uncommon. In active leaks, change in the characteristics of the headache in a short period should raise suspicion about unexpected developments including sinus thrombosis. Often requires anticoagulation.52

Bibrachial amyotrophy

Typically associated with elongated extra-arachnoid fluid collection, often in the ventral aspect of the cord. May extend along many spinal levels. Weakness and atrophy of a few contiguous cervical myotomes. Sensory findings minimal or absent. May mimic motor neuron disease.53

Superficial siderosis

Rare, remote complication. Often elongated extra-arachnoid fluid collections are seen ventral to the cord, similar to those seen in bibrachial amyotrophy.54

Syringomyelia

Rare. Can be very small or quite extensive. Often associated with significant descent of cerebellar tonsils.

CSF = cerebrospinal fluid.

(Case 10-2), cerebral venous and venous sinus thrombosis, superficial siderosis, bibrachial amyotrophy, and syringomyelia. Related references are given in the same table. When symptoms linger after an apparently successful treatment of a CSF leak, the reason may be an incomplete cessation of the leak, development of complications, or development of an entirely different type of headache, such as tension or migraine headache. RECURRENCE OF CSF LEAKS CSF leaks can recur at variable intervals and with variable frequency from previous leaks; they are not uncommon, although their incidence is not well established. Information based on surgical referrals may not be applicable Continuum (Minneap Minn) 2015;21(4):1086–1108

to the entire group of patients with recurrences. Those patients with stigmata of disorders of the connective tissue matrix may be at a somewhat higher risk. ORTHOSTATIC HEADACHES WITHOUT CSF LEAK As pointed out earlier, not all headaches associated with spontaneous CSF leaks are orthostatic, and not all orthostatic headaches are due to CSF leaks. Orthostatic headaches have been noted in association with other conditions, including postural tachycardia syndrome (POTS),55 effects of surgery for Chiari malformation, the ‘‘syndrome of the trephined’’ (a deteriorating neurologic syndrome sometimes encountered in survivors of large craniectomies, often conducted

KEY POINT

h Lingering symptoms after apparently successful treatment of a CSF leak may point to incomplete cessation of the leak, the development of complications, or a different type of headache etiology, including tension or migraine headaches.

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as a lifesaving measure in treatment of increasing cerebral edema),56 increased compliance of the dural sac,57 and possibly rare cases of colloid cyst of the third ventricle.4 CONCLUSION Spontaneous intracranial hypotension is almost always the result of spontaneous CSF leakage. Past theories of increased absorption or decreased production of CSF have never been substantiated. The overwhelming majority of spontaneous leaks occur at the level of spine, frequently in preexisting areas of dural weakness from an underlying disorder of the connective tissue matrix. In contrast to posttraumatic and postsurgical leaks, spontaneous leaks from the skull base are very infrequent. The triad of orthostatic headaches, diffuse pachymeningeal enhancement on MRI, and low CSF opening pressure is considered the hallmark of diagnosis, but variability in just about every aspect of this disorder is substantial. With the broadening of the overall spectrum of this entity and increasing number of diagnosed cases, there has been an increase in referrals of atypical, uncertain, and doubtful cases, which, in turn, bring new challenges. In this disorder, decreased CSF volume rather than decreased pressure is the core pathophysiologic factor. The rate of CSF leakage may vary, and rapid-flow and slow-flow leaks each present diagnostic challenges. Epidural blood patch has emerged as the treatment of choice when initial conservative measures have failed. Epidural blood patch may be single level (often), bilevel (sometimes), and multilevel (in selected cases). Surgery aimed at stopping the leak is considered when lessinvasive measures have failed and when the exact site of the leak has been determined, or when imaging studies show the anatomy of the leak is such that success from epidural blood patch is judged to be unlikely. CSF leaks may recur (not

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uncommon), and complications (some uncommon, some rare) may develop. REFERENCES 1. Mokri B, Schievink WI. Headache associated with abnormalities in intracranial structure or function: low cerebrospinal fluid pressure headache. In: Silberstein SD, Lipton RB, Dodick DW, editors. Wolff’s headache and other head pain. 8th ed. New York: Oxford University Press, 2007:513Y531. 2. Johnston M. The importance of lymphatics in cerebrospinal fluid transport. Lymphat Res Biol 2003;1(1):41Y44. doi:10.1089/ 15396850360495682. 3. Miller JD. Volume and pressure in the craniospinal axis. Clin Neurosurg 1975;22:76Y105. 4. Mokri B. Spontaneous low pressure, low CSF volume headaches: spontaneous CSF leaks. Headache 2013;53(7):1034Y1053. doi:10.1111/head.12149. 5. Hebert-Blouin MN, Mokri B, Shin AY, et al. Cerebrospinal fluid volume-depletion headaches in patients with traumatic brachial plexus injury. J Neurosurg 2013;118(1):149Y154. doi:10.3171/ 2012.9.JNS112368. 6. Cilluffo JM, Gomez MR, Reese DF, et al. Idiopathic (‘‘congenital’’) spinal arachnoid diverticula. Clinical diagnosis and surgical results. Mayo Clin Proc 1981;56(2):93Y101. 7. Schievink WI, Torres VE. Spinal meningeal diverticula in autosomal dominant polycystic kidney disease. Lancet 1997;349(9060):1223Y1224. 8. Pyeritz RE, Fishman EK, Bernhardt BA, Siegelman SS. Dural ectasia is a common feature of the Marfan syndrome. Am J Hum Genet 1988;43(5):726Y732. 9. Cohen-Gadol AA, Mokri B, Piepgras DG, et al. Surgical anatomy of dural defects in spontaneous spinal cerebrospinal fluid leaks. Neurosurgery 2006;58(4 suppl 2):ONS-238-45. doi:10.1227/01.NEU.0000204712.16099.FB. 10. Mokri B, Maher CO, Sencakova D. Spontaneous CSF leaks: underlying disorder of connective tissue. Neurology 2002;58(5): 814Y816. doi:10.1212/WNL.58.5.814. 11. Schrijver I, Schievink WI, Godfrey M, et al. Spontaneous spinal cerebrospinal fluid leaks and minor skeletal features of Marfan syndrome: a microfibrillopathy. J Neurosurg 2002;96(3):483Y489. 12. Mokri B. Familial occurrence of spontaneous spinal CSF leaks: underlying connective tissue disorder. Headache 2008;48(1):146Y149. doi:10.1111/j.1526-4610.2007.00979.x.

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13. Eross EJ, Dodick DW, Nelson KD, et al. Orthostatic headache syndrome with CSF leak secondary to bony pathology of the cervical spine. Cephalalgia 2002;22(6):439Y443. doi:10.1046/j.1468-2982.2002.00385.x. 14. Winter SC, Maartens NF, Anslow P, Teddy PJ. Spontaneous intracranial hypotension due to thoracic disc herniation. Case report. J Neurosurg 2002;96(3 suppl):343Y345. 15. Mokri B. Spontaneous CSF leaks: low CSF volume syndromes. Neurol Clin 2014;32(2): 397Y422. doi:10.1016/j.ncl.2013.11.002. 16. Schaltenbrand G. Normal and pathological physiology of the cerebrospinal fluid circulation. Lancet 1953;1(6765):805Y808. doi:10.1016/S0140-6736(53)91948-5. 17. Marcelis J, Silberstein SD. Spontaneous low cerebrospinal fluid pressure headache. Headache 1990;30(4):192Y196. doi:10.1111/ j.1526-4610.1990.hed3004192.x. 18. Mokri B. Spontaneous CSF leaks mimicking benign exertional headaches. Cephalalgia 2002;22(10):780Y783. doi:10.1046/ j.1468-2982.2002.00400.x. 19. Schievink WI, Wijdicks EF, Meyer FB, Sonntag VK. Spontaneous intracranial hypotension mimicking aneurysmal subarachnoid hemorrhage. Neurosurgery 2001;48(3):513Y516. 20. Leep Hunderfund AN, Mokri B. Second-half-of-the-day headache as a manifestation of spontaneous CSF leak. J Neurol 2012;259(2):306Y310. doi:10.1007/ s00415-011-6181-z. 21. Mokri B, Aksamit AJ, Atkinson JL. Paradoxical postural headaches in cerebrospinal fluid leaks. Cephalalgia 2004;24(10):883Y887. doi:10.1111/j.1468-2982.2004.00763.x. 22. Portier F, de Minteguiaga C, Racy E, et al. Spontaneous intracranial hypotension: a rare cause of labyrinthine hydrops. Ann Otol Rhinol Laryngol 2002;111(9):817Y820. 23. Horton JC, Fishman RA. Neurovisual findings in the syndrome of spontaneous intracranial hypotension from dural cerebrospinal fluid leak. Ophthalmology 1994;101(2):244Y251. 24. Hong M, Shah GV, Adams KM, et al. Spontaneous intracranial hypotension causing reversible frontotemporal dementia. Neurology 2002;58(8):1285Y1287. doi:10.1212/WNL.58.8.1285. 25. Mokri B. Movement disorders associated with spontaneous CSF leaks: a case series. Cephalalgia 2014;34(14):1134Y1141. doi:10.1177/0333102414531154. Continuum (Minneap Minn) 2015;21(4):1086–1108

26. Fay T. Mechanism of headache. Arch Neurol Psychiatry 1937;37:471Y474. 27. Mokri B. Intracranial hypertension after treatment of spontaneous cerebrospinal fluid leaks. Mayo Clin Proc 2002;77(11):1241Y1246. doi:10.4065/77.11.1241. 28. Mokri B. Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid hypovolemiaVevolution of a concept. Mayo Clin Proc 1999;74(11): 1113Y1123. doi:10.4065/74.11.1113. 29. Mokri B. Radioisotope cisternography in spontaneous CSF leaks: interpretations and misinterpretations. Headache 2014;54(8): 1358Y1368. doi:10.1111/head.12421. 30. Schievink WI, Moser FG, Maya MM. CSF-venous fistula in spontaneous intracranial hypotension. Neurology 2014;83(5):472Y473. doi:10.1212/WNL.0000000000000639. 31. Starling A, Hernandez F, Hoxworth JM, et al. Sensitivity of MRI of the spine compared with CT myelography in orthostatic headache with CSF leak. Neurology 2013;81(20):1789Y1792. doi:10.1212/01.wnl.0000435555.13695.22. 32. Adler F, Gupta N, Hess CP, et al. Intraosseous CSF fistula in a patient with Gorham disease resulting in intracranial hypotension. AJNR Am J Neuroradiol 2011;32(11):E198YE200. doi:10.3174/ajnr.A2413. 33. Mokri B. The Monro-Kellie hypothesis: applications in CSF volume depletion. Neurology 2001;56(12):1746Y1748. doi:10.1212/WNL.56.12.1746. 34. Luetmer PH, Mokri B. Dynamic CT myelography: a technique for localizing high-flow spinal cerebrospinal fluid leaks. AJNR Am J Neuroradiol 2003;24(8):1711Y1714. 35. Hoxworth JM, Trentman TL, Kotsenas AL, et al. The role of digital subtraction myelography in the diagnosis and localization of spontaneous spinal CSF leaks. AJR Am J Roentgenol 2012;199(3):649Y653. doi:10.2214/AJR.11.8238. 36. Akbar JJ, Luetmer PH, Schwartz KM, et al. The role of MR myelography with intrathecal gadolinium in localization of spinal CSF leaks in patients with spontaneous intracranial hypotension. AJNR Am J Neuroradiol 2012;33(3):535Y540. doi:10.3174/ajnr.A2815. 37. Vilmig ST, Titus F. Low cerebrospinal fluid pressure. In: Olesen J, Tfelt-Hansen P, Welch KMA, eds. The headache. New York: Oxford University Press, 2001:417Y433. 38. Rice GG, Dabbs CH. The use of peridural and subarachnoid injections of saline solution in the treatment of severe postspinal headache. Anesthesiology 1950;11(1):17Y23. www.ContinuumJournal.com

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39. Binder DK, Dillon WP, Fishman RA, Schmidt MH. Intrathecal saline infusion in the treatment of obtundation associated with spontaneous intracranial hypotension: technical case report. Neurosurgery 2002;51(3):830Y836. 40. Duffy PJ, Crosby ET. The epidural blood patch. Resolving the controversies. Can J Anaesth 1999;46(9):878Y886. doi:10.1007/BF03012979. 41. Sencakova D, Mokri B, McClelland RL. The efficacy of epidural blood patch in spontaneous CSF leaks. Neurology 2001; 57(10):1921Y1923. doi:10.1212/WNL.57.10.1921. 42. Crul BJ, Gerritse BM, van Dongen RT, Schoonderwaldt HC. Epidural fibrin glue injection stops persistent postdural puncture headache. Anesthesiology 1999;91(2):576Y577. 43. Gerritse BM, van Dongen RT, Crul BJ. Epidural fibrin glue injection stops persistent cerebrospinal fluid leak during long-term intrathecal catheterization. Anesth Analg 1997;84(5):1140Y1141. 44. Franzini A, Messina G, Nazzi V, et al. Spontaneous intracranial hypotension syndrome: a novel speculative physiopathological hypothesis and a novel patch method in a series of 28 consecutive patients. J Neurosurg 2010;112(2):300Y306. doi:10.3171/2009.6.JNS09415. 45. Kranz PG, Gray L, Taylor JN. CT-guided epidural blood patching of directly observed or potential leak sites for the targeted treatment of spontaneous intracranial hypotension. AJNR Am J Neuroradiol 2011;32(5):832Y838. doi:10.3174/ajnr.A2384. 46. Freeman ED, Hoelzer BC, Eldrige JS, Moeschler SM. Fibrin glue to treat spinal fluid leaks associated with intrathecal drug systems. Pain Pract 2014;14(6):570Y576. doi:10.1111/papr.12151. 47. Gladstone JP, Nelson K, Patel N, Dodick DW. Spontaneous CSF leak treated with percutaneous CT-guided fibrin glue. Neurology 2005;64(10):1818Y1819. doi:10.1212/01.WNL.0000162029.96759.D2. 48. Schievink WI, Georganos SA, Maya MM, et al. Anaphylactic reactions to fibrin sealant

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injection for spontaneous spinal CSF leaks. Neurology 2008;70(11):885Y887. doi:10.1212/ 01.wnl.0000265400.54810.13. 49. Schievink WI, Morreale VM, Atkinson JL, et al. Surgical treatment of spontaneous spinal cerebrospinal fluid leaks. J Neurosurg 1998;88(2):243Y246. 50. de Noronha RJ, Sharrack B, Hadjivassiliou M, Romanowski CA. Subdural haematoma: a potentially serious consequence of spontaneous intracranial hypotension. J Neurol Neurosurg Psychiatry 2003;74(6): 752Y755. doi:10.1136/jnnp.74.6.752. 51. Kelley GR, Johnson PL. Sinking brain syndrome: craniotomy can precipitate brainstem herniation in CSF hypovolemia. Neurology 2004;62(1):157. doi:10.1212/ WNL.62.1.157. 52. Berroir S, Grabli D, Heran F, et al. Cerebral sinus venous thrombosis in two patients with spontaneous intracranial hypotension. Cerebrovasc Dis 2004;17(1):9Y12. 53. Deluca GC, Boes CJ, Krueger BR, et al. Ventral intraspinal fluid-filled collection secondary to CSF leak presenting as bibrachial amyotrophy. Neurology 2011;76(16):1439Y1440. doi:10.1212/WNL. 0b013e3182166e6f. 54. Kumar N, McKeon A, Rabinstein AA, et al. Superficial siderosis and CSF hypovolemia: the defect (dural) in the link. Neurology 2007;69(9):925Y926. doi:10.1212/01.wnl. 0000267847.69896.be. 55. Mokri B, Low PA. Orthostatic headaches without CSF leak in postural tachycardia syndrome. Neurology 2003;61(7):980Y982. doi:10.1212/01.WNL.0000085868.37963.7D. 56. Mokri B. Orthostatic headaches in the syndrome of the trephined: resolution following cranioplasty. Headache 2010;50(7):1206Y1211. doi:10.1111/ j.1526-4610.2010.01715.x. 57. Leep Hunderfund AN, Mokri B. Orthostatic headache without CSF leak. Neurology 2008;71(23):1902Y1906. doi:10.1212/ 01.wnl.0000336655.07617.e0.

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Spontaneous Intracranial Hypotension.

Spontaneous intracranial hypotension results from CSF volume depletion, nearly always from spontaneous CSF leaks. Spontaneous intracranial hypotension...
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