Spontaneous Spinal Cerebrospinal Fluid Leaks and Intracranial Hypotension

CLINICAL REVIEW CLINICIAN’S CORNER

Wouter I. Schievink, MD Context Spontaneous intracranial hypotension is caused by spontaneous spinal ce- PATIENT PRESENTS WITH A rebrospinal fluid (CSF) leaks and is known for causing orthostatic headaches. It is an new headache that occurs important cause of new headaches in young and middle-aged individuals, but initial shortly after assuming an up- misdiagnosis is common. right position and is re- Objective To summarize existing evidence regarding the epidemiology, pathophysi- lievedA by lying down. Although such a ology, diagnosis, and management of spontaneous spinal CSF leaks and intracranial positional headache pattern is well- hypotension. known following a diagnostic lumbar Evidence Acquisition MEDLINE (1966-2005) and OLDMEDLINE (1950-1965) were puncture, the spontaneous onset of an searched using the terms intracranial hypotension, CSF leak, low pressure headache, orthostatic headache is not well recog- and CSF hypovolemia. Reference lists of these articles and ongoing investigations in nized and the patient may be diag- this area were used as well. nosed with migraine, tension head- Evidence Synthesis Spontaneous intracranial hypotension is caused by single or ache, viral meningitis, or malingering. multiple spinal CSF leaks. The incidence has been estimated at 5 per 100 000 per year, This has been a typical scenario for with a peak around age 40 years. Women are affected more commonly than men. Mechanical factors combine with an underlying connective tissue disorder to cause many patients experiencing spontane- 1 the CSF leaks. An orthostatic headache is the prototypical manifestation but other head- ous intracranial hypotension. The ache patterns occur as well, and associated symptoms are common. Typical magnetic spontaneous form of intracranial hy- resonance imaging findings include subdural fluid collections, enhancement of the pachy- potension was first described in 1938,2 meninges, engorgement of venous structures, pituitary hyperemia, and sagging of the and much has been learned about this brain (mnemonic: SEEPS). Myelography is the study of choice to identify the spinal syndrome, particularly since the early CSF leak. Treatments include bed rest, epidural blood patching, percutaneous place- 1990s,3-15 but an initial misdiagnosis re- ment of fibrin sealant, and surgical CSF leak repair, but outcomes have been poorly mains the norm. Unfamiliarity with studied and no management strategies have been studied in properly controlled ran- spontaneous intracranial hypotension domized trials. among physicians in general and the Conclusions Spontaneous intracranial hypotension is not rare but it remains under- unusually varied spectrum of clinical diagnosed. The spectrum of clinical and radiographic manifestations is varied, with di- and radiographic manifestations may all agnosis largely based on clinical suspicion, cranial magnetic resonance imaging, and myelography. Numerous treatment options are available, but much remains to be learned contribute to a delay in diagnosis that about this disorder. often is measured in months or even JAMA. 2006;295:2286-2296 www.jama.com years and decades.1 EVIDENCE ACQUISITION also were used. Clinical trials were not spontaneous intracranial hypotension The material covered in this review is available, and prospective studies were is not that rare and has to be consid- based on a systematic review of journal selected over retrospective studies. Se- ered an important cause of new daily articles in MEDLINE (1966-2005) and lected articles were largely those pub- persistent headaches, particularly OLDMEDLINE (1950-1965) using the lished within the past 10 years and hav- among young and middle-aged indi- terms intracranial hypotension, CSF leak, ing adequate documentation and relevant viduals. In the past, our knowledge re- low pressure headache, and CSF hypovo- clinical information, but older articles were also included if they were com- Author Affiliation: Maxine Dunitz Neurosurgical In- lemia. Reference lists of these articles stitute, Cedars-Sinai Medical Center, Los Angeles, Calif. and ongoing investigations in this area monly referenced and highly regarded. Corresponding Author: Wouter I. Schievink, MD, Max- ine Dunitz Neurosurgical Institute, Cedars-Sinai Medi- EVIDENCE SYNTHESIS cal Center, 8631 W Third St, Suite 800E, Los Ange- See also Patient Page. les, CA 90048 ([email protected]). Epidemiology Clinical Review Section Editor: Michael S. Lauer, MD. CME available online at Once considered an exceedingly rare We encourage authors to submit papers for consid- www.jama.com eration as a Clinical Review. Please contact Michael disorder, recent evidence suggests that S. Lauer, MD, at [email protected].

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garding spontaneous intracranial hy- Comprehensive population-based epi- symptoms typically is in the fourth or potension was derived from case reports demiologic studies, however, are not yet fifth decade of life, with a peak inci- only, and no epidemiologic data were available. In the past, spontaneous in- dence around age 40 years, but chil- available. In a community-based study tracranial hypotension was probably dren and elderly persons also may be conducted in 1994, the prevalence of more frequently underdiagnosed than affected.1-16 spontaneous intracranial hypotension it is now, and it is unlikely that there was estimated at 1 per 50 000.16 In a has been an actual increase in its inci- Etiology and Pathogenesis more recent emergency department– dence, although that possibility can- Spontaneous intracranial hypotension based study (2003-2004),17 spontane- not be entirely excluded. is caused by spontaneous spinal cere- ous intracranial hypotension was half Spontaneous intracranial hypoten- brospinal fluid (CSF) leaks. Because as common as spontaneous subarach- sion affects women more frequently spinal CSF leaks generally do not noid hemorrhage, for an estimated than men, with a female-male ratio cause any local symptoms, they annual incidence of 5 per 100 000. of approximately 2:1.1-16 Onset of remain undetected unless actively

Figure 1. Spinal Cord Anatomy and Intraoperative Photograph With Corresponding Line Drawing of a Complex Meningeal Diverticulum Arising From a Thoracic Nerve Root Sleeve in a 27-Year-Old Woman

A Spinal Cord Anatomy Epidural Venous Plexus Spinal Nerve Root (Covered in Dura) Transverse Spinous Process Process Dura Mater Spinal Meninges Arachnoid Subarachnoid Pia Mater Space

T8 T9 T10

Dorsal Root Spinal Nerve Root Ventral Root

B Complex Meningeal Diverticulum

INTRAOPERATIVE VIEW

TRANSVERSE SECTION

POSTERIOR Multilobed Meningeal Dura Mater Multilobed Meningeal Diverticulum Diverticulum Arachnoid

0.5 cm

DURA MATER LEFT RIGHT

Spinal Nerve Root (Covered in Dura)

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ver to large amounts of CSF spontane- A distinct and uncommon cause of Box 1. Connective Tissue ously pouring out into the paraspinal spontaneous intracranial hypotension Disorders Associated soft tissues. not associated with a primary dural de- With Spontaneous Spinal There is good evidence to suggest fect is the presence of osseous spinal pa- Cerebrospinal Fluid Leaks that a generalized connective tissue thology. A congenital osseous spur,35 as and Intracranial Hypotension disorder plays a crucial role in the well as acquired degenerative disk dis- 36-39 Named Syndromes development of spontaneous spinal ease piercing the dura, has been CSF leaks. First reported in 1994,20 described. Marfan syndrome this association has been confirmed by Before precise imaging was able Ehlers-Danlos syndrome type II numerous subsequent studies.11,22-25 to detect the underlying spinal CSF Autosomal dominant polycystic Based on physical examination alone, leak, some authors speculated that kidney disease evidence for an underlying generalized spontaneous intracranial hypotension Unnamed Syndromes/ connective tissue disorder is found in resulted from decreased CSF secretion Associations about two thirds of patients.25 This or generalized CSF hyperabsorption, Isolated skeletal features of Marfan group of disorders is heterogeneous, but there are no data to support such syndrome possibly affecting different compo- alternate mechanisms. It has been pos- Isolated joint hypermobility nents of the dural extracellular matrix tulated that a decrease in CSF volume, (BOX 1). Isolated joint hypermobility rather than in CSF pressure, may be Joint hypermobility with fascial thinning is found in approximately two fifths the final common pathway in the of patients with spontaneous intracra- pathophysiology of spontaneous intra- Spontaneous retinal detachment nial hypotension and may be associ- cranial hypotension.40 Therefore, ated with attenuation of the dorsal “spontaneous CSF hypovolemia” has muscular fascia, complicating surgi- been introduced as an alternative looked for in a patient suspected of cal wound closure.25 Approximately one term.40 However, this is an oversimpli- spontaneous intracranial hypotension. fifth of patients with spontaneous fication. For example, loss of CSF vol- Also, unlike CSF rhinorrhea or otor- intracranial hypotension have subtle ume also occurs with spontaneous rhea, there is no risk of meningitis skeletal manifestations of Marfan syn- CSF rhinorrhea or otorrhea, but the because the CSF is directly absorbed drome, such as tall stature, arachno- typical imaging and clinical features of into the sterile spinal epidural venous dactyly, highly arched palate, and spontaneous intracranial hypotension plexus or paraspinal soft tissues and is joint hypermobility, but none of the rarely, if ever, occur under those cir- therefore not exposed to the external other stigmata of the syndrome.20,22,23,25 cumstances. The final common path- milieu. These patients do not harbor muta- way is probably not CSF hypovolemia The precise cause of spontaneous spi- tions in the Marfan syndrome gene but rather an altered distribution of nal CSF leaks remains largely un- (FBN1) encoding fibrillin 1, but a craniospinal elasticity due to spinal known, but an underlying structural defect of microfibrils, important loss of CSF,41 and “spontaneous spinal weakness of the spinal meninges gen- components of the extracellular ma- CSF leak” is the preferred descriptive erally is suspected.11 A history of a more trix associated with fibrillin, has term. or less trivial traumatic event preced- been demonstrated.22,23 Less fre- ing the onset of symptoms can be elic- quently, spontaneous intracranial Clinical Presentation ited in about one third of patients, sug- hypotension occurs in well-character- Positional Headache. The prototypi- gesting a role for mechanical factors as ized, generalized connective tissue dis- cal manifestation of spontaneous in- well.4,18,19 The dural weakness predis- orders such as Marfan syndrome,26-29 tracranial hypotension is an ortho- poses to the formation of dural defects Ehlers-Danlos syndrome type II,25 and static headache. Such a headache that allow CSF to leak into the epidu- autosomal dominant polycystic kid- generally occurs or worsens within 15 ral space. A wide variety of dural de- ney disease.30 Spinal meningeal diver- minutes of assuming the upright posi- fects may be observed at the time of sur- ticula also have been described in neu- tion, as reflected by the revised Inter- gery, ranging from simple dural holes rofibromatosis type 131,32 and Lehman national Classification of Headache Dis- or rents to complex fragile meningeal syndrome.33,34 Finally, some patients orders criteria (BOX 2),42 but in some diverticula or even complete absence of with spontaneous intracranial hypo- patients this lag period may be as long the dura that normally covers the spi- tension have a personal or family his- as several hours. Improvement of the nal nerve root (FIGURE 1).11,16,20,21 The tory of spontaneous retinal detach- headache after lying down is less vari- volume of the CSF leak is quite vari- ment at an early age, suggesting the able and occurs within 15 to 30 min- able as well, ranging from a minimal presence of a generalized connective utes. The headache may be diffuse or amount of seeping CSF only detect- tissue disorder affecting both dura and localized to the frontal, temporal, or— able when applying a Valsalva maneu- retina.11 most commonly—the occipital or sub-

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occipital regions. The headache may be throbbing or nonthrobbing and is rarely Box 2. Diagnostic Criteria for Headache Due to Spontaneous Spinal unilateral. Some patients use descrip- CSF Leak and Intracranial Hypotension According to the tive terms for their headaches, such as International Classification of Headache Disorders, 2nd Ed42 the feeling of “an ice cube in an empty A. Diffuse and/or dull headache that worsens within 15 minutes after sitting or glass” or a “pulling sensation from my standing, fulfilling criterion D and with Ն1 of the following: head down to my neck,” offering a clue 1. Neck stiffness to the diagnosis. Additional clues may 2. Tinnitus be the patient’s recumbent position in 3. Hypacusia the physician’s office or a pillow they 4. Photophobia carry along to allow them to lie down 5. Nausea comfortably. The initial onset of head- B. At least 1 of the following: ache generally is gradual or subacute, 1. Evidence of low CSF pressure on MRI (eg, pachymeningeal enhancement) reaching maximal intensity in several 2. Evidence of CSF leakage on conventional myelography, CT myelography, minutes to hours, but it may be instan- or cisternography taneous.43 Patients with such a “thun- Ͻ 3. CSF opening pressure 60 mm H2O in sitting position derclap” headache often will be sus- C. No history of dural puncture or other cause of CSF fistula pected of having a subarachnoid D. Headache resolves within 72 hours after epidural blood patching hemorrhage and may undergo invasive testing, such as cerebral angiogra- Abbreviations: CSF, cerebrospinal fluid; CT, computed tomography; MRI, magnetic resonance imaging. phy. The severity of the headache var- ies widely; many mild cases probably remain undiagnosed, whereas other patients are incapacitated and unable to when lying down.49,50 Intermittent head- associated with tinnitus or a disturbed engage in any useful activity while aches, presumably caused by intermit- sense of balance. These symptoms upright. tent spinal CSF leaks, may occur at in- may be explained by direct transmis- The headache is a direct result of the tervals of weeks, months, or even years. sion of the abnormal CSF pressure to downward displacement of the brain Finally,some patients deny having any that in the perilymph.51 Alternatively, due to loss of CSF buoyancy, causing headache, usually when other symp- downward displacement of the brain traction on pain-sensitive structures, toms of spontaneous intracranial hy- may cause stretching of the eighth particularly the dura. An alternative potension predominate the clinical nerve complex (cochlear and vestibu- mechanism involves compensatory di- picture. lar nerves). This latter mechanism lation of the pain-sensitive intracra- Because of the wide variety of head- may also explain other manifestations nial venous structures. ache patterns, magnetic resonance im- of spontaneous intracranial hypoten- It should be noted that not all ortho- aging (MRI) should be considered for sion, such as visual blurring or visual static headaches are caused by sponta- all patients with unexplained head- field defects (optic nerve or chiasm), neous spinal CSF leaks, and other di- ache to evaluate for spontaneous intra- diplopia (abducens or, rarely, trochlear agnoses should be considered.44,45 cranial hypotension. A differential di- and oculomotor nerves), facial numb- Other Headache Patterns. Al- agnosis of headache due to spontaneous ness or pain (trigeminal nerve), facial though a postural headache is the clini- intracranial hypotension is provided in weakness or spasm (facial nerve), and cal hallmark of spontaneous intracra- the TABLE. dysgeusia (chorda tympani or glosso- nial hypotension, it is well known that Miscellaneous Symptoms. In addi- pharyngeal nerve).11,12,52-55 Distortion the posture-related component often, tion to headaches, a wide variety of of the pituitary stalk has been impli- but not invariably,becomes less promi- other symptoms have been reported cated as a cause of hyperprolactinemia nent or even disappears over time when in spontaneous intracranial hypoten- and galactorrhea associated with spon- the underlying spinal CSF leak re- sion. Posterior neck pain or stiffness, taneous intracranial hypotension.56 mains untreated.11 Rarely, the reverse nausea, and vomiting are the most Severe displacement of the brain may occurs with a nonpositional headache common, being reported by approxi- even result in a decreased level of con- preceding a typical orthostatic head- mately 50% of patients, and suggest sciousness due to diencephalic hernia- ache. Some patients have no posture- meningeal irritation, particularly when tion. Although uncommon, numerous related component to their headache photophobia or phonophobia also is well-documented cases have now been from the onset,46,47 while others report present.1,11,12 The next most common reported from around the world, and exertional headaches,48 headaches that symptom is a change in hearing, spontaneous intracranial hypotension mainly occur at the end of the day, or which may be described as “echoing” should be considered in the differen- even paradoxical headaches that worsen or as “being underwater” and may be tial diagnosis of stupor and coma, par-

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ticularly in otherwise healthy young standing of spontaneous intracranial subdural fluid collections, (2) en- and middle-aged adults.57-62 Other hypotension and has greatly facilitated hancement of the pachymeninges, rare manifestations of spontaneous the ability to arrive at the diagnosis (3) engorgement of venous structures, intracranial hypotension include with confidence without having to (4) pituitary hyperemia, and (5) sag- parkinsonism, ataxia, and cerebellar resort to invasive procedures, such as ging of the brain (mnemonic: SEEPS) hemorrhage.50,63 Dementia is a rare spinal puncture or intracranial pres- (FIGURE 2). complication of spontaneous intracra- sure monitoring. Recognition of the A relationship between subdural nial hypotension,64 but subtle cogni- MRI features probably is the most hematomas and intracranial hypoten- tive deficits are not rare and often important factor responsible for the sion has long been debated in the lit- are not recognized until cognition ever-increasing number of patients erature, and accumulation of subdural improves following successful treat- diagnosed with spontaneous intracra- fluid was the first recognized imaging ment of the spinal CSF leak. Spinal nial hypotension since the early 1990s. feature of spontaneous intracranial manifestations include interscapular On the other hand, an incomplete hypotension.65-71 Subdural fluid collec- pain or, rarely, local back pain at the understanding of the variability tions are common in spontaneous site of the CSF leak; quadriplegia; and of MRI findings has resulted in intracranial hypotension, occurring in radicular symptoms due to stretching the diagnosis of spontaneous intracra- approximately 50% of patients.71 Most of cervical spinal nerve roots or dila- nial hypotension being erroneously of these subdural fluid collections rep- tion of the epidural venous plexus. excluded in patients with normal resent hygromas and are thin, bilat- findings. eral, located over the cerebral convexi- Diagnosis The 5 characteristic imaging fea- ties, and do not cause any appreciable Cranial MRI. Magnetic resonance tures of spontaneous intracranial mass effect. They may also be seen in imaging has revolutionized the under- hypotension visible on MRI are (1) the posterior fossa, particularly over

Table. Differential Diagnosis of Headache Due to Spontaneous Spinal Cerebrospinal Fluid Leak and Intracranial Hypotension* Connective Typical Age Female-Male Tissue Thunderclap Confirmatory Headache Disorder at Onset, y Ratio Disorders† Headache Features Headache Associated Features Testing Primary New daily persistent 15-50 2:1 No Bilateral more common No Nausea, fatigue, None headache (Mean, 35) than unilateral preceding viral Migraine or tension-type illness dominant Secondary Spontaneous 20-60 2:1 Yes Bilateral much more Yes Visual/aural changes, MRI, LP, intracranial (Mean, 40) common than unilateral meningismus, myelogram hypotension Improved with recumbancy, cranial nerve but variable dysfunction Subarachnoid Ͼ20 1.5:1 Yes Bilateral more common Yes Meningismus, cranial CT, LP hemorrhage (Mean, 50) than unilateral nerve dysfunction, Onset instantaneous seizure in most, but may be gradual Carotid/vertebral 20-70 1:1 Yes Unilateral much more Yes Horner syndrome, Angiography artery dissection (Mean, 45) common than bilateral cranial nerve Often with neck pain dysfunction, pulsatile tinnitus Cerebral venous Any age 3:1 No Bilateral more common Yes Seizure, papilledema, MRI/MRV, sinus thrombosis than unilateral (but visual changes, angiography unilateral when cranial nerve headache is only sign) dysfunction Benign intracranial 20-40 8:1 No Bilateral much more No Papilledema, visual LP hypertension (Mean, 30) common than unilateral changes, abducens Worse in recumbancy nerve palsy Posttraumatic Any age 1.5:1 No Bilateral much more No Dizziness, None headache common than unilateral neuropsychological Tension-type, often after symptoms mild head injury Meningitis Any age 1:1 No Bilateral Yes Fever, meningismus, LP systemic illness Abbreviations: CT, computed tomography; LP, lumbar puncture; MRI, magnetic resonance imaging; MRV, magnetic resonance venography. *The headache of spontaneous spinal cerebrospinal fluid leak and intracranial hypotension is best considered under the category of new daily persistent headache. Such headaches have an abrupt onset, often within minutes or hours but by definition within 3 days, and are present on most if not all days thereafter, typically in individuals without a prior history of headache. †Including autosomal dominant polycystic kidney disease, Ehlers-Danlos syndrome, and Marfan syndrome.

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the cerebellar convexities or in the ret- Figure 2. Pretreatment and Posttreatment Magnetic Resonance Imaging roclival space. Subdural hematomas with varying degrees of mass effect Before Treatment After Treatment also are not uncommon in spontane- A ous intracranial hypotension and are about half as frequent as subdural hygromas (FIGURE 3).71 Fortunately, most of these subdural hematomas can be managed with treatment directed at the underlying spinal CSF leak without the need for crani- otomy.71 Only rarely do the subdural hematomas require evacuation, and if the underlying CSF leak is left untreated, the risk of a recurrent subdural hematoma is high.68,69,71 Enhancement of the pachymeninges has become the most well-known imaging abnormality of spontaneous intracranial hypotension. The en- B hancement is diffuse, nonnodular, involves both supratentorial and infratentorial compartments, and spares the leptomeninges.72,73 Small, thin-walled dilated blood vessels in the subdural zone are the pathological substrate for the enhancement.12 The relation between the enhancement and spontaneous intracranial hypotension has been believed to be so close that the term “syndrome of orthostatic headache and diffuse pachymeningeal gadolinium enhancement” was coined.12 However, up to 20% of patients with spontaneous intracranial C hypotension never develop enhancement, or any of the other abnormalities, on MRI.40,74,75 Engorgement of venous structures is most readily detected when it affects the dural venous sinuses or large cerebral veins.76-78 It is rarely the only or the most striking imaging feature of spontaneous hypotension and often is only de- tectable when pretreatment and posttreatment images are compared. Pituitary hyperemia is a recently described imaging feature of spontaneous intracranial hypotension.79-82 The A, Axial fluid-attenuated inversion recovery views showing resolution of bilateral subdural hematomas (black pituitary hyperemia may become quite arrowheads) and engorgement of the superior sagittal sinus (yellow arrowhead) in a 35-year-old man. B, Axial striking and mimic a pituitary tumor or T1-weighted views after intravenous administration of gadolinium showing resolution of enhancement of the hyperplasia. pachymeninges (arrowheads) in a 39-year-old woman. C, Sagittal T1-weighted views showing resolution of sagging of the brain (flattening of the pons with obliteration of the prepontine cistern [black arrowheads] and Sagging or downward displacement downward displacement of the cerebellar tonsils mimicking a Chiari malformation [arrow]) and hyperemia/ of the brain is a very specific imaging enlargement of the pituitary gland (yellow arrowheads) in a 41-year-old woman. Also note restoration of ventricular size following treatment in all panels. finding of spontaneous intracranial

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lowed by MRI) has been shown to be Figure 3. Axial T2-Weighted Magnetic Resonance Image in a 39-Year-Old Man the study of choice to accurately define the location and extent of a CSF A B leak (FIGURE 4).11 The leak may vary from a small amount of contrast tracking along a single nerve root to extensive bilateral collections of contrast within the paraspinal soft tissues. Single or multiple meningeal diverticula may be demonstrated, but they are frequently below the level of detection of myelography and not uncovered until the time of surgery. The majority of CSF leaks are found at the cervicothoracic junction or along the thoracic spine. Frequently, multiple simultaneous CSF leaks are demonstrated. Retrospinal collec- A, Imaging shows subdural hygromas (arrowheads). B, The patient’s spinal cerebrospinal fluid leaks were left tions of contrast at C1-C2 should not untreated and bilateral subdural hematomas developed (arrowheads). be mistaken for the actual site of the CSF leak.85 Delayed imaging may be hypotension and may be accompanied mas. Subdural hematomas may be required to visualize slow or inter- by ventricular collapse.8,73 Several fea- caused by tearing of bridging veins or mittent leaks, and ultra-early (ie, tures can be identified, such as efface- rupture of the dilated thin-walled blood immediately following injection of ment of perichiasmatic cisterns with vessels in the subdural zone. Sagging contrast) computed tomography may bowing of the optic chiasm over the of the brain is caused by the loss of CSF be required to identify the site of pituitary fossa; effacement of the pre- buoyancy. rapid high-volume leaks. pontine cistern with flattening of the Improvement of abnormalities on The fear of cerebral herniation caused pons against the clivus; and descent of MRI can be expected within days to by performing a myelogram is entirely the cerebellar tonsils, which may weeks of successful treatment of the theoretical and has never been docu- mimic a Chiari type 1 malformation. CSF leak. Clinical improvement gen- mented. Not only is the dural hole made Sagging of the brain in spontaneous erally precedes that demonstrated on by the lumbar puncture relatively small, intracranial hypotension may be MRI, and in some patients—particu- but CSF pressure is already low.Aggra- attributed to coexisting subdural fluid larly those who have not received spe- vation of symptoms is reported by only collections, but the degree of sagging cific treatment for their CSF leak— approximately 5% of patients and is generally is out of proportion to any considerable clinical improvement is generally mild. mass effect from the subdural fluid shown over time, whereas the MRI ab- Radionuclide Cisternography. Ra- collections. normalities persist. Small subdural hy- dionuclide cisternography has been Most of the MRI features of sponta- gromas resolve within days or weeks, used extensively in the evaluation of neous intracranial hypotension can but large subdural hematomas may re- spontaneous intracranial hypotension be explained as compensatory changes quire up to 3 months to resolve. but is of relatively limited useful- related to the loss of CSF volume. Cranial Computed Tomography. Al- ness.11,86,87 Typicalfindings include early According to the Monroe-Kellie hy- though not as conclusive as MRI, com- accumulation of tracer in the kidneys pothesis, the sum of the volumes puted tomography may suggest the di- and bladder, slow ascent along the spi- of intracranial blood, CSF, and cere- agnosis by showing subdural fluid nal axis, and a paucity of activity over bral tissue must remain constant in collections or obliteration of subarach- the cerebral convexities. However, the an intact cranium.73 Thus, the loss of noid cisterns and ventricular col- exact site of the CSF leak remains ob- CSF from the spine can be compen- lapse.66,83,84 Computed tomography can scure in as many as one third of pa- sated for by an increase of the vascular thus be of important diagnostic value, tients.11 Radionuclide cisternography re- component, accounting for the pachy- particularly in the emergency depart- mains useful when the diagnosis of meningeal enhancement, engorgement setting. intracranial hypotension is in doubt and ment of venous structures, and pitu- Myelography. Myelography with myelography results are normal. itary hyperemia; or by an increase in iodinated contrast followed by thin- Spinal MRI. In the past, relatively the intracranial CSF component, cut computed tomography of the scant attention was given to spinal accounting for the subdural hygro- entire spine (or with gadolinium fol- MRI in the diagnosis of spontaneous

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intracranial hypotension, mainly Lumbar Puncture. Typically,CSF op- mia that is probably due to increased per- because it is not particularly effective ening pressure is less than 60 mm H2O meability of dilated meningeal blood in localizing the CSF leak. However, (reference range, 65-195 mm H2O) and vessels and a decrease of CSF flow in the numerous spinal manifestations of can be unmeasurable or even negative.9 lumbar subarachnoid space. spontaneous intracranial hypotension However, some patients have consis- have now been described, such as tently normal CSF opening pressures.11 Treatment and Outcome dilated epidural or intradural veins, Examination of CSF often demon- Although data are lacking, it is often dural enhancement, meningeal diver- strates abnormal results, showing a pri- stated that many cases of spontaneous ticula, extrathecal CSF collections, marily lymphocytic pleocytosis (up to intracranial hypotension resolve spon- syringomyelia, and retrospinal C1-C2 200 cells/mm3), an elevated protein con- taneously without any specific therapy. fluid collections.88-94 tent (up to 1000 mg/dL), or xanthochro- Fortunately, several options are avail-

Figure 4. Postmyelography Computed Tomography Scans—Demonstration of Spinal Cerebrospinal Fluid (CSF) Leaks

B C

A, Multiple thoracic CSF leaks associated with meningeal diverticula in a 23-year-old woman (arrowheads). Also note contrast within the right kidney (black arrowhead). Images taken at T6-7, T10-11, and T11-12. B, Bilateral CSF leaks at the cervicothoracic junction extending into the paraspinal soft tissues in a 54-year-old woman (arrowheads). Image taken at C7-T1. C, Contained CSF collection anterolateral to the thoracic spinal cord in a 58-year-old man (arrowhead). Image taken at T3-4.

Figure 5. Postmyelography Computed Tomography Scans—Results of Treatment

A B C

A, Results of an epidural blood patch in a 46-year-old woman. Note posterior midline location of epidural blood patch (arrowhead). Image taken at T7-8. B, Percu- taneous placement of a fibrin sealant in a 48-year-old woman. Note lateral location of fibrin sealant (arrowhead). Image taken at T6-7. C, Surgical clipping (arrowheads) of bilateral meningeal diverticula in a 23-year-old woman. Image taken at T12-L1.

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able to treat patients with spontane- If epidural blood patches fail to pro- while those with normal initial MRI ous intracranial hypotension who seek vide relief, a directed epidural blood findings and a diffuse multilevel spi- medical attention (FIGURE 5). How- patch or percutaneous placement of final CSF leak have a poor prognosis.100 ever, none of the treatments have been brin sealant is recommended. These Some patients have persistent symp- evaluated by randomized clinical trials. therapies require that the exact site of toms following treatment, in spite of A purely conservative approach con- the CSF leak be known, and place- documented resolution of CSF leak- sists of bed rest, oral hydration, a gen- ment of fibrin sealant probably pro- age. Such patients may have residual al- erous caffeine intake, and use of an ab- vides the best chance of alleviating tered CSF dynamics or small residual dominal binder. Given enough time, symptoms. In my experience, about one CSF leaks below the level of detection this treatment is probably effective in third of patients for whom epidural of current imaging techniques. many patients. However, symptoms blood patching has not been effective Author Contributions: Dr Schievink had full access to may be debilitating, and more timely re- experience relief with the percutane- all of the data in the study and takes responsibility for sults may be desired. Administration of ous placement of fibrin sealant, thereby the integrity of the data and the accuracy of the data 97 analysis. steroids, intravenous caffeine, or the- avoiding surgery. Study concept and design; acquisition of data; analy- ophylline all have been advocated as Surgical treatment is reserved for sis and interpretation of data; drafting of the manuscript; critical revision of the manuscript for impor- specific treatments for spontaneous in- those patients in whom these nonsur- tant intellectual content; administrative, technical, or tracranial hypotension, but their effec- gical measures have failed. Surgical re- material support; study supervision: Schievink. tiveness is limited. pair of CSF leak is safe and often suc- Financial Disclosures: None reported. The mainstay of treatment is the ceeds in providing relief for those injection of autologous blood into the patients in whom a structural abnor- REFERENCES spinal epidural space, the so-called epi- mality or focal CSF leak is identi- 1. Schievink WI. Misdiagnosis of spontaneous intra- 95,96 16,20,21 cranial hypotension. Arch Neurol. 2003;60:1713-1718. dural blood patch. Relief of symp- fied. 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