Curr Pain Headache Rep (2014) 18:425 DOI 10.1007/s11916-014-0425-4
UNCOMMON HEADACHE SYNDROMES (J AILANI, SECTION EDITOR)
Low-Pressure/Spinal Fluid Leak Headache Roderick C. Spears
Published online: 24 April 2014 # Springer Science+Business Media New York 2014
Abstract Low cerebrospinal fluid (CSF) pressure results in neurologic deficits, of which the most common manifestation is headache. Typically, the headache is postural – and specifically, orthostatic – in presentation. There are three hypotheses to explain the occurrence of headache associated with low CSF fluid. The first is traction on pain-sensitive intracranial and meningeal structures; the second is CSF hypovolemia; and the third is spinal loss of CSF resulting in increased compliance at the caudal end of the CSF space. Spontaneous intracranial hypotension (SIH), once believed to be rare, is now more commonly recognized. It is typically associated with orthostatic headache (although initially it may not be) and one or more other symptoms such as alterations in hearing, nausea, vomiting, neck stiffness, diplopia, and visual field cuts. Magnetic resonance imaging (MRI) of the brain with gadolinium is the first study of choice, which typically reveals diffuse pachymeningeal enhancement and, frequently, cerebellar tonsillar descent and posterior fossa crowding. Epidural blood patch (EBP) is the treatment of choice. Surgery and epidural fibrin glue injection are options for those who fail conservative therapy and/or EBP.
Keywords Low cerebral spinal fluid . Spontaneous intracranial hypotension (SIH) . Epidural blood patch (EBP) . Orthostatic headache . Cerebral spinal fluid leak . Chronic daily headache (CDH) . Lumbar puncture (LP)
This article is part of the Topical Collection on Uncommon Headache Syndromes R. C. Spears (*) Center for Headache Management, Crozer Chester Medical Center, 1 Medical Center Blvd., Upland, PA 19013, USA e-mail: [email protected]
Introduction Intracranial pressure is significantly affected by the production, absorption, and flow of CSF. The most common neurologic symptom associated with alterations in CSF pressure is headache. Low CSF pressure most commonly results in orthostatic headache and occurs following a lumbar puncture (LP), although there has been increasing recognition of similar headaches from SIH. While SIH classically presents with the triad of orthostatic headache, low CSF pressure, and diffuse meningeal enhancement on brain MRI, there have been cases with non-orthostatic headache, normal CSF pressure, or no evidence of diffuse meningeal enhancement [1]. Lumbar puncture was introduced in 1891 by Heinrich Quincke for the treatment of hydrocephalus [2]. In the same year, W. Essex Wynter reported four cases of tubercular meningitis in which lumbar punctures were performed to relieve pressure [3]. The first post-LP headaches were reported by August Bier and August Hildebrandt in 1898 [4]. Bier proposed that continuous leakage of CSF fluid through the dural puncture site was the cause of the headache. This belief, which is still held today, postulates that leakage of CSF through the dural rent made by the needle exceeds the rate of CSF production, resulting in low CSF volume and pressure [5]. In 1938, Georg Schaltenbrand was the first to propose the idea of spontaneous low CSF pressure, although he used the term aliquorrhea [6]. Schaltenbrand described a headache syndrome virtually identical to post-LP headaches and proposed three possible mechanisms to explain the syndrome: increased CSF absorption, CSF leakage through small tears, and decreased CSF production. The current belief is that the majority of SIH cases are as a result of CSF leakage that likely occurs secondary to spontaneous rupture of an arachnoid membrane [7]. While many posttraumatic or postsurgical CSF leaks can occur from the skull base, the majority of spontaneous leaks are found at the spinal level. This review will discuss the differences between
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post-LP headache and headache secondary to spontaneous intracranial hypotension. It will also discuss the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of both syndromes.
Pathophysiology The pathophysiology of post-LP headache appears straightforward. Normally, the CSF supports the brain so that a brain weight of 1,500 g in air is reduced to 48 g in CSF [8]. As CSF pressure decreases, there is reduction in buoyancy of the brain’s supportive cushion, which causes the brain to descend in the posterior fossa, causing traction on its anchoring and supporting structures [9–12]. This description also applies to low CSF-pressure headache secondary to SIH. Additional possibilities for non-spontaneous CSF hypovolemia include a true hypovolemic state. This would include traumatic CSF leaks such as definite trauma from sports injuries or motor vehicle accidents; or, as previously mentioned, thecal holes and rents from LPs, epidural catheters, and spinal and cranial surgeries, including sinus surgery and skull base surgery; and finally, proximal brachial plexus avulsion injuries and/or nerve root avulsion injuries. CSF shunt overdrainage could also result in CSF hypovolemia [13••]. The etiology of headache pain is believed to be secondary to three primary pathophysiologic changes. The first is traction on pain-sensitive structures such as the sensory nerves and bridging veins [11], which is exaggerated in the upright position. To compensate for the low CSF pressure, secondary vasodilation of the cerebral vessels occurs, leading to increased brain volume [10]. Second, Mokri proposed that CSF hypovolemia rather than CSF hypotension is the cause of headache [1, 13••]. This is supported by patients with clinical and radiographic features typical of orthostatic headache that are found to have normal CSF pressure [1, 14–16]. It is thought that CSF pressures, imaging abnormalities, and clinical manifestations are variables that are dependent upon CSF volume [17]. The third hypothesis is that spinal leaks of CSF result in increased compliance at the caudal end of the spinal CSF space, and that this abnormal distribution leads to craniospinal elasticity, which causes headache [18]. The underlying etiology of SIH is more challenging and less obvious than that of low CSF-pressure headache from a known secondary cause, and the exact cause of spontaneous CSF leaks is often unclear. One of the most recent hypotheses proposes that these patients have a connective tissue abnormality and that this underlying abnormality leads to weakness of the dura, which may play a role in the development of spontaneous low CSF pressure. This is supported by studies demonstrating connective tissue abnormalities in patients with spontaneous CSF leaks [19, 20]. In one study, dermal fibroblast cultures in patients with spontaneous CSF leaks were
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found to be deficient of fibrillin, elastin, or both [21]. The specific dural abnormality identified in the literature is meningeal diverticula, which is often seen in patients with CSF leaks [22]. Marfan’s syndrome is an example of a connective tissue disorder with abnormalities in fibrillin and elastin where dural sac ectasia, meningeal diverticula, and CSF leaks have been described [20, 23, 24]. The contribution of trivial trauma to the development of spontaneous CSF leaks in the setting of underlying dural weakness is controversial, with some authors reporting occurrences in a minority of patients and others stating that it rarely occurs. Examples of trivial trauma include coughing, lifting, pulling, pushing, sexual intercourse or orgasm, and falling.
Epidemiology There is not a great deal of data in the literature with regard to the incidence of low CSF-pressure headache. In 2006, Schievink published a systematic review of the subject utilizing a MEDLINE search from 1950 to 2005, in which he found the following: 1) the annual incidence was estimated to be 5/100,000; 2) the peak age of incidence was around 40 years; and 3) women were affected more than men by a ratio of 2:1 [25•]. These data support the belief that low CSF-pressure headache is not rare but that it remains under-diagnosed.
Clinical Features As previously mentioned, headache is the most common clinical manifestation of low CSF pressure. The headache is commonly present when upright and relieved in recumbency, although this may not always occur. The location of the pain is most often bilateral [26], and may be frontal, occipital, or holocephalic [27]. In rare cases, the headache will begin as unilateral or focal but will eventually become holocephalic, depending upon the amount of time in an upright position. The quality of the pain is often described as throbbing or a pressure-like sensation, but may also be a dull pain, and severity ranges from mild to extremely severe [25•]. The headache is often triggered by sitting or standing, Valsalvatype maneuvers, coughing, sneezing, head movement, high altitude, and jugular venous compression [28]. As previously mentioned, recumbency initially alleviates the headache, typically within minutes, but this feature may disappear completely as the patient becomes chronic. Headaches of SIH have a variety of presentations: 1) chronic daily headache or head pressure sensation that is lingering and non-orthostatic [13••]; 2) initially, chronic daily headache associated with cervical or interscapular pain, or those pains in isolation, followed by orthostatic headache [13••]; 3) development of chronic daily headache following
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several months of orthostatic headache [13••]; 4) thunderclap headache [29]; 5) headaches that are present in recumbency and are relieved in an upright position (called paradoxical postural headache [13••]; 6) headaches that occur exclusively during the second half of the day [13••]; 7) exertional headaches [13••]; 8) intermittent headaches believed to be associated with intermittent CSF leaks [13••]; and 9) no headache, although testing supports the occurrence of CSF leak [13••]. There are many features associated with low CSF-pressure headache, the most common of which are neck pain or stiffness, nausea, and vomiting, which are found in approximately 50 % of patients [25•]. Additional associated features include anorexia, photophobia, hiccups, vertigo, dizziness, hyperacusis [1], echoing [30], tinnitus [27], blurred vision, diplopia, diaphoresis, transient visual obscurations [8], dysgeusia [27], and staggering gait [5]. Other non-headache clinical manifestations rarely occur with this syndrome and are likely due to compression of the brain or structures of the spinal cord. They are as follows: 1) ataxia, which is proposed to be related to the posterior fossa; 2) galactorrhea and hyperprolactinemia, which are thought to be related to the pituitary stalk; 3) quadriparesis, believed to be related to the brainstem and cervical spinal cord [31]; 4) movement disorders such as parkinsonism and chorea, which are proposed to be related to the deep midline structures [32, 33]; 5) cerebellar hemorrhage, thought to be related to the cerebellar bridging veins [31]; 6) hypoactive/hypoalert behavior, which is believed to be related to the pons and midbrain [34]; 7) personality change, memory decline, apathy, frontotemporal dementia-like presentation [35, 36]; 8) decreased level of consciousness, stupor, and coma, thought to be related to the diencephalon [37–39]; and 9) impaired bowel or bladder control [40]. Cerebellar hemorrhage is not readily reversible, but all other features resolve with successful treatment of the CSF leak.
Diagnosis Most patients that present with low CSF-pressure headache will be found to have normal neurological examinations [41]. Abnormalities that have been reported in the literature include unilateral or bilateral abducens palsies and visual field defects [8] as well as bradycardia [11]. Due to the detection of pachymeningeal thickening on MRI, many patients have multiple CSF examinations to identify the etiology of this finding, be it inflammatory, infectious, or neoplastic. As a result, much has been learned about the CSF findings in patients with CSF leaks, not the least of which is the variability that is seen [13••]. In the majority of patients, the opening CSF pressure is low, typically in the range of 0–70 mm of H2O [9]. In approximately 25 % of cases, the opening pressure is in the normal range, which is 60–200 mm of H2O. LPs can be
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difficult to obtain in patients with SIH secondary to low pressure. Rarely, CSF pressure can actually be negative, below atmospheric pressure, during an LP. In these cases, CSF is often blood-tinged, which is believed to be secondary to the low pressure previously mentioned as well as the presence of dilated epidural venous plexus. Otherwise, CSF is clear. Protein levels are typically normal to high, with values as high as 100 mg/dL. The presence of red blood cells and lymphocytic pleocytosis is common. Glucose levels, cytology, and microbiology should all be normal [13••]. Our understanding of SIH has been significantly enhanced with advances in MRI technology. Most patients with SIH will have an abnormal finding on MRI of the brain; 20 % of patients will have a normal MRI [41]. The most common head MRI abnormalities of CSF leaks are as follows. 1) Diffuse pachymeningeal enhancement; uninterrupted, nonnodular, no leptomeningeal involvement, can be thick or thin [42]. 2) Descent or “sagging” of the brain. This MRI phenomenon includes the following: descent of cerebellar tonsil to or below the level of the foramen magnum [43]; descent of the brainstem, which may occur without descent of the cerebellar tonsils [13••]; an increase in the anterior/posterior diameter of the brainstem, which is believed to be secondary to distortion of the brainstem [13••]; crowding of the posterior fossa, as well as flattening of the optic chiasm and flattening of the anterior pons [13••]. 3) Subdural hygromas and, less frequently, hematomas. This is believed to be secondary to rupture of the bridging veins as CSF volume decreases [44, 45]. 4) Enlargement of the pituitary gland which has been associated with the previously mentioned phenomenon of flattening of the optic chiasm and the increase of the anterior/posterior diameter of the brainstem [46, 47]. 5) Engorgement of cerebral venous sinuses [48]. 6) Finally, decrease in the size of the ventricles. The major features of SIH found on brain MRI are summarized by using the acronym SEEPS, which stands for Subdural fluid collections, Enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain [25•]. The most common spinal MRI abnormalities of CSF leaks are as follows: 1) extra-arachnoid fluid collections that may extend along several spinal levels [48–50]; 2) extradural extravasation of fluid, including extending to paraspinal soft tissues; 3) single or multiple meningeal diverticula of various sizes and any level; 4) dural enhancement [51]; and finally 5) engorgement of the spinal epidural venous plexus. Following MRI, radioisotope cisternography is usually the next study of choice if there is a high clinical suspicion for SIH but a normal MRI. The radioisotope that is used is indium111. A lumbar puncture is performed, and the radioisotope is introduced intrathecally. The dynamics of the radioisotope are followed by sequential scanning at various intervals up to 24 or even 48 hours. If a patient has a CSF leak, radioactivity should not extend beyond the basal cisterns at 24 hours, or
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even at 48 hours. This is the most common and most reliable abnormality found on cisternography in active CSF leaks, although it is considered to be “indirect evidence.” Much less common is parathecal activity at a specific level suspected to be a CSF leak, and while it is less common, it is considered to be “direct evidence.” If meningeal diverticula are large enough, they may appear as parathecal activity on a cisternogram, which is difficult to distinguish from an actual CSF leak on this particular study. Finally, the early appearance of radioactivity in the kidneys and urinary bladder is fairly common. One would expect to see this in less than 4 hours, while on a normal study it would be 6 to 24 hours. This is considered to be “indirect evidence” of a CSF leak. Computed tomographic (CT) myelography is the most accurate study to identify the exact site of the CSF leak [52]. CT myelography also reveals extra-arachnoid fluid collections, extradural egress of contrast in the paraspinal tissues, meningeal diverticula, and dilated nerve root sleeves. Obtaining early and delayed cuts at each spinal level is recommended to address both fast and slow CSF leaks. CT myelography is most often used in the setting of a patient who has failed epidural blood patch and requires either surgical repair or fibrin glue injection. Magnetic resonance (MR) myelography is a growing cutting-edge technology that may serve as an alternative to CT myelography.
Treatment Treatment of low CSF-pressure headache whether secondary to a known cause or SIH, usually begins with conservative measures. These include bed rest, which is typically desired by patients with the most significant orthostatic headaches, coffee intake, hydration, and time. Most of these measures are based on long-term practices of treating post-LP headaches, and they will work in the majority of patients with low CSFpressure headaches. When dealing with SIH, some patients resolve in two weeks, while others continue to have headaches for several months or, rarely, even years [41]. Medications are also tried prior to procedural options, including analgesics for pain relief, caffeine and theophylline via intravenous infusions, and corticosteroids. The response to caffeine and theophylline is unpredictable, with some patients doing very well and others not responding. Corticosteroids provide relief in some patients, although the effects are transient. Epidural blood patch is currently the treatment of choice in patients who have not responded to conservative measures [52], and the mechanism of action is believed to be twofold. The first is volume replacement by compression of the dural sac that is believed to cause the immediate effect, and the second is sealing of the dural defect, which may be delayed from the first action. This may result in a waxing and waning clinical course, such as initial resolution of symptoms,
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followed by recurrence in 24 to 48 hours, then followed by gradual improvement. A previous failure of epidural blood patch should not preclude a repeat, should that be necessary, as many patients require several epidural blood patches to achieve freedom from symptoms. Epidural blood patch has an efficacy of only 30 % in SIH, but it is significantly higher in post-LP headache, at 90 % following first attempt [53, 54]. One of the reasons for this variance is that the target site for the epidural blood patch is typically close to the site of the leak, and while the site of the leak is likely in the posterior dura in post-LP headache, it is postulated that the site of the CSF leak in SIH is at the nerve root sleeves or nerve root axilla. Another reason for the difference is what is called the dural defect in SIH, which is the idea that an unsupported arachnoid in a preexisting zone of attenuated dura loses its integrity, causing CSF to leak from one or more sites. The use of fibrin glue to repair the leak is a technique that has shown promise. Once the location of the CSF leak has been identified, surgery is effective. Other treatment options that have had less reliable results include intrathecal fluid injection, epidural saline infusion, intravenous saline infusions, epidural infusion of dextran, and the use of an abdominal binder. There are five major complications of spontaneous CSF leaks that the reader should be aware of, as almost all of them will require corrective action. The first is subdural hematoma. These vary in size, and can be small and asymptomatic or large, resulting in compression of the brain. In the case of very large subdural hematoma, surgical intervention is warranted [55, 56]. Cerebral venous thrombosis (CVT) is another potential complication. Fortunately, this is an uncommon occurrence, but a rapid change in headache characteristics should prompt further investigation. CVT is typically treated with anticoagulation. The third is rebound intracranial hypertension, which is typically seen following successful treatment by epidural blood patch or surgery [57]. Another complication is bibrachial amyotrophy, where the patient presents clinically with weakness and atrophy of a few sequential myotomal distributions of the upper extremities. This is associated with mild asymmetry similar to what is seen in motor neuron disease [58], and is associated with extra-arachnoid fluid collection in the ventral aspect of the spinal cord, primarily in the cervical and thoracic regions, although it can extend to the lumbar region as well [13••]. Finally, superficial siderosis is a rare complication, although it has been described in association with spinal CSF leaks [59, 60]. This is characterized by extra-arachnoid fluid collections similar to those seen in bibrachial amyotrophy involving the ventral spinal cord.
Conclusions While headache associated with low CSF pressure is not rare, the diagnosis can be missed, especially in the case of
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spontaneous CSF leak where there is no history of dural puncture or significant trauma. The literature supports the theory that patients with an underlying connective tissue disorder may be at increased risk of developing a spontaneous CSF leak. Aside from the characteristic clinical presentation, which can vary somewhat, there are also several imaging modalities as well as LP to assist with diagnosis. Treatment options range from conservative to surgical repair. The natural course of this disorder in the majority of patients is spontaneous resolution, although the timeline to resolution is variable. Major complications are possible in conjunction with CSF leaks and, less commonly, following successful treatment. Compliance with Ethics Guidelines Conflict of Interest Dr. Roderick C. Spears declares no potential conflict of interest relevant to this article. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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UNCOMMON HEADACHE SYNDROMES (J AILANI, SECTION EDITOR)
Low-Pressure/Spinal Fluid Leak Headache Roderick C. Spears
Published online: 24 April 2014 # Springer Science+Business Media New York 2014
Abstract Low cerebrospinal fluid (CSF) pressure results in neurologic deficits, of which the most common manifestation is headache. Typically, the headache is postural – and specifically, orthostatic – in presentation. There are three hypotheses to explain the occurrence of headache associated with low CSF fluid. The first is traction on pain-sensitive intracranial and meningeal structures; the second is CSF hypovolemia; and the third is spinal loss of CSF resulting in increased compliance at the caudal end of the CSF space. Spontaneous intracranial hypotension (SIH), once believed to be rare, is now more commonly recognized. It is typically associated with orthostatic headache (although initially it may not be) and one or more other symptoms such as alterations in hearing, nausea, vomiting, neck stiffness, diplopia, and visual field cuts. Magnetic resonance imaging (MRI) of the brain with gadolinium is the first study of choice, which typically reveals diffuse pachymeningeal enhancement and, frequently, cerebellar tonsillar descent and posterior fossa crowding. Epidural blood patch (EBP) is the treatment of choice. Surgery and epidural fibrin glue injection are options for those who fail conservative therapy and/or EBP.
Keywords Low cerebral spinal fluid . Spontaneous intracranial hypotension (SIH) . Epidural blood patch (EBP) . Orthostatic headache . Cerebral spinal fluid leak . Chronic daily headache (CDH) . Lumbar puncture (LP)
This article is part of the Topical Collection on Uncommon Headache Syndromes R. C. Spears (*) Center for Headache Management, Crozer Chester Medical Center, 1 Medical Center Blvd., Upland, PA 19013, USA e-mail: [email protected]
Introduction Intracranial pressure is significantly affected by the production, absorption, and flow of CSF. The most common neurologic symptom associated with alterations in CSF pressure is headache. Low CSF pressure most commonly results in orthostatic headache and occurs following a lumbar puncture (LP), although there has been increasing recognition of similar headaches from SIH. While SIH classically presents with the triad of orthostatic headache, low CSF pressure, and diffuse meningeal enhancement on brain MRI, there have been cases with non-orthostatic headache, normal CSF pressure, or no evidence of diffuse meningeal enhancement [1]. Lumbar puncture was introduced in 1891 by Heinrich Quincke for the treatment of hydrocephalus [2]. In the same year, W. Essex Wynter reported four cases of tubercular meningitis in which lumbar punctures were performed to relieve pressure [3]. The first post-LP headaches were reported by August Bier and August Hildebrandt in 1898 [4]. Bier proposed that continuous leakage of CSF fluid through the dural puncture site was the cause of the headache. This belief, which is still held today, postulates that leakage of CSF through the dural rent made by the needle exceeds the rate of CSF production, resulting in low CSF volume and pressure [5]. In 1938, Georg Schaltenbrand was the first to propose the idea of spontaneous low CSF pressure, although he used the term aliquorrhea [6]. Schaltenbrand described a headache syndrome virtually identical to post-LP headaches and proposed three possible mechanisms to explain the syndrome: increased CSF absorption, CSF leakage through small tears, and decreased CSF production. The current belief is that the majority of SIH cases are as a result of CSF leakage that likely occurs secondary to spontaneous rupture of an arachnoid membrane [7]. While many posttraumatic or postsurgical CSF leaks can occur from the skull base, the majority of spontaneous leaks are found at the spinal level. This review will discuss the differences between
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post-LP headache and headache secondary to spontaneous intracranial hypotension. It will also discuss the pathophysiology, epidemiology, clinical features, diagnosis, and treatment of both syndromes.
Pathophysiology The pathophysiology of post-LP headache appears straightforward. Normally, the CSF supports the brain so that a brain weight of 1,500 g in air is reduced to 48 g in CSF [8]. As CSF pressure decreases, there is reduction in buoyancy of the brain’s supportive cushion, which causes the brain to descend in the posterior fossa, causing traction on its anchoring and supporting structures [9–12]. This description also applies to low CSF-pressure headache secondary to SIH. Additional possibilities for non-spontaneous CSF hypovolemia include a true hypovolemic state. This would include traumatic CSF leaks such as definite trauma from sports injuries or motor vehicle accidents; or, as previously mentioned, thecal holes and rents from LPs, epidural catheters, and spinal and cranial surgeries, including sinus surgery and skull base surgery; and finally, proximal brachial plexus avulsion injuries and/or nerve root avulsion injuries. CSF shunt overdrainage could also result in CSF hypovolemia [13••]. The etiology of headache pain is believed to be secondary to three primary pathophysiologic changes. The first is traction on pain-sensitive structures such as the sensory nerves and bridging veins [11], which is exaggerated in the upright position. To compensate for the low CSF pressure, secondary vasodilation of the cerebral vessels occurs, leading to increased brain volume [10]. Second, Mokri proposed that CSF hypovolemia rather than CSF hypotension is the cause of headache [1, 13••]. This is supported by patients with clinical and radiographic features typical of orthostatic headache that are found to have normal CSF pressure [1, 14–16]. It is thought that CSF pressures, imaging abnormalities, and clinical manifestations are variables that are dependent upon CSF volume [17]. The third hypothesis is that spinal leaks of CSF result in increased compliance at the caudal end of the spinal CSF space, and that this abnormal distribution leads to craniospinal elasticity, which causes headache [18]. The underlying etiology of SIH is more challenging and less obvious than that of low CSF-pressure headache from a known secondary cause, and the exact cause of spontaneous CSF leaks is often unclear. One of the most recent hypotheses proposes that these patients have a connective tissue abnormality and that this underlying abnormality leads to weakness of the dura, which may play a role in the development of spontaneous low CSF pressure. This is supported by studies demonstrating connective tissue abnormalities in patients with spontaneous CSF leaks [19, 20]. In one study, dermal fibroblast cultures in patients with spontaneous CSF leaks were
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found to be deficient of fibrillin, elastin, or both [21]. The specific dural abnormality identified in the literature is meningeal diverticula, which is often seen in patients with CSF leaks [22]. Marfan’s syndrome is an example of a connective tissue disorder with abnormalities in fibrillin and elastin where dural sac ectasia, meningeal diverticula, and CSF leaks have been described [20, 23, 24]. The contribution of trivial trauma to the development of spontaneous CSF leaks in the setting of underlying dural weakness is controversial, with some authors reporting occurrences in a minority of patients and others stating that it rarely occurs. Examples of trivial trauma include coughing, lifting, pulling, pushing, sexual intercourse or orgasm, and falling.
Epidemiology There is not a great deal of data in the literature with regard to the incidence of low CSF-pressure headache. In 2006, Schievink published a systematic review of the subject utilizing a MEDLINE search from 1950 to 2005, in which he found the following: 1) the annual incidence was estimated to be 5/100,000; 2) the peak age of incidence was around 40 years; and 3) women were affected more than men by a ratio of 2:1 [25•]. These data support the belief that low CSF-pressure headache is not rare but that it remains under-diagnosed.
Clinical Features As previously mentioned, headache is the most common clinical manifestation of low CSF pressure. The headache is commonly present when upright and relieved in recumbency, although this may not always occur. The location of the pain is most often bilateral [26], and may be frontal, occipital, or holocephalic [27]. In rare cases, the headache will begin as unilateral or focal but will eventually become holocephalic, depending upon the amount of time in an upright position. The quality of the pain is often described as throbbing or a pressure-like sensation, but may also be a dull pain, and severity ranges from mild to extremely severe [25•]. The headache is often triggered by sitting or standing, Valsalvatype maneuvers, coughing, sneezing, head movement, high altitude, and jugular venous compression [28]. As previously mentioned, recumbency initially alleviates the headache, typically within minutes, but this feature may disappear completely as the patient becomes chronic. Headaches of SIH have a variety of presentations: 1) chronic daily headache or head pressure sensation that is lingering and non-orthostatic [13••]; 2) initially, chronic daily headache associated with cervical or interscapular pain, or those pains in isolation, followed by orthostatic headache [13••]; 3) development of chronic daily headache following
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several months of orthostatic headache [13••]; 4) thunderclap headache [29]; 5) headaches that are present in recumbency and are relieved in an upright position (called paradoxical postural headache [13••]; 6) headaches that occur exclusively during the second half of the day [13••]; 7) exertional headaches [13••]; 8) intermittent headaches believed to be associated with intermittent CSF leaks [13••]; and 9) no headache, although testing supports the occurrence of CSF leak [13••]. There are many features associated with low CSF-pressure headache, the most common of which are neck pain or stiffness, nausea, and vomiting, which are found in approximately 50 % of patients [25•]. Additional associated features include anorexia, photophobia, hiccups, vertigo, dizziness, hyperacusis [1], echoing [30], tinnitus [27], blurred vision, diplopia, diaphoresis, transient visual obscurations [8], dysgeusia [27], and staggering gait [5]. Other non-headache clinical manifestations rarely occur with this syndrome and are likely due to compression of the brain or structures of the spinal cord. They are as follows: 1) ataxia, which is proposed to be related to the posterior fossa; 2) galactorrhea and hyperprolactinemia, which are thought to be related to the pituitary stalk; 3) quadriparesis, believed to be related to the brainstem and cervical spinal cord [31]; 4) movement disorders such as parkinsonism and chorea, which are proposed to be related to the deep midline structures [32, 33]; 5) cerebellar hemorrhage, thought to be related to the cerebellar bridging veins [31]; 6) hypoactive/hypoalert behavior, which is believed to be related to the pons and midbrain [34]; 7) personality change, memory decline, apathy, frontotemporal dementia-like presentation [35, 36]; 8) decreased level of consciousness, stupor, and coma, thought to be related to the diencephalon [37–39]; and 9) impaired bowel or bladder control [40]. Cerebellar hemorrhage is not readily reversible, but all other features resolve with successful treatment of the CSF leak.
Diagnosis Most patients that present with low CSF-pressure headache will be found to have normal neurological examinations [41]. Abnormalities that have been reported in the literature include unilateral or bilateral abducens palsies and visual field defects [8] as well as bradycardia [11]. Due to the detection of pachymeningeal thickening on MRI, many patients have multiple CSF examinations to identify the etiology of this finding, be it inflammatory, infectious, or neoplastic. As a result, much has been learned about the CSF findings in patients with CSF leaks, not the least of which is the variability that is seen [13••]. In the majority of patients, the opening CSF pressure is low, typically in the range of 0–70 mm of H2O [9]. In approximately 25 % of cases, the opening pressure is in the normal range, which is 60–200 mm of H2O. LPs can be
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difficult to obtain in patients with SIH secondary to low pressure. Rarely, CSF pressure can actually be negative, below atmospheric pressure, during an LP. In these cases, CSF is often blood-tinged, which is believed to be secondary to the low pressure previously mentioned as well as the presence of dilated epidural venous plexus. Otherwise, CSF is clear. Protein levels are typically normal to high, with values as high as 100 mg/dL. The presence of red blood cells and lymphocytic pleocytosis is common. Glucose levels, cytology, and microbiology should all be normal [13••]. Our understanding of SIH has been significantly enhanced with advances in MRI technology. Most patients with SIH will have an abnormal finding on MRI of the brain; 20 % of patients will have a normal MRI [41]. The most common head MRI abnormalities of CSF leaks are as follows. 1) Diffuse pachymeningeal enhancement; uninterrupted, nonnodular, no leptomeningeal involvement, can be thick or thin [42]. 2) Descent or “sagging” of the brain. This MRI phenomenon includes the following: descent of cerebellar tonsil to or below the level of the foramen magnum [43]; descent of the brainstem, which may occur without descent of the cerebellar tonsils [13••]; an increase in the anterior/posterior diameter of the brainstem, which is believed to be secondary to distortion of the brainstem [13••]; crowding of the posterior fossa, as well as flattening of the optic chiasm and flattening of the anterior pons [13••]. 3) Subdural hygromas and, less frequently, hematomas. This is believed to be secondary to rupture of the bridging veins as CSF volume decreases [44, 45]. 4) Enlargement of the pituitary gland which has been associated with the previously mentioned phenomenon of flattening of the optic chiasm and the increase of the anterior/posterior diameter of the brainstem [46, 47]. 5) Engorgement of cerebral venous sinuses [48]. 6) Finally, decrease in the size of the ventricles. The major features of SIH found on brain MRI are summarized by using the acronym SEEPS, which stands for Subdural fluid collections, Enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain [25•]. The most common spinal MRI abnormalities of CSF leaks are as follows: 1) extra-arachnoid fluid collections that may extend along several spinal levels [48–50]; 2) extradural extravasation of fluid, including extending to paraspinal soft tissues; 3) single or multiple meningeal diverticula of various sizes and any level; 4) dural enhancement [51]; and finally 5) engorgement of the spinal epidural venous plexus. Following MRI, radioisotope cisternography is usually the next study of choice if there is a high clinical suspicion for SIH but a normal MRI. The radioisotope that is used is indium111. A lumbar puncture is performed, and the radioisotope is introduced intrathecally. The dynamics of the radioisotope are followed by sequential scanning at various intervals up to 24 or even 48 hours. If a patient has a CSF leak, radioactivity should not extend beyond the basal cisterns at 24 hours, or
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even at 48 hours. This is the most common and most reliable abnormality found on cisternography in active CSF leaks, although it is considered to be “indirect evidence.” Much less common is parathecal activity at a specific level suspected to be a CSF leak, and while it is less common, it is considered to be “direct evidence.” If meningeal diverticula are large enough, they may appear as parathecal activity on a cisternogram, which is difficult to distinguish from an actual CSF leak on this particular study. Finally, the early appearance of radioactivity in the kidneys and urinary bladder is fairly common. One would expect to see this in less than 4 hours, while on a normal study it would be 6 to 24 hours. This is considered to be “indirect evidence” of a CSF leak. Computed tomographic (CT) myelography is the most accurate study to identify the exact site of the CSF leak [52]. CT myelography also reveals extra-arachnoid fluid collections, extradural egress of contrast in the paraspinal tissues, meningeal diverticula, and dilated nerve root sleeves. Obtaining early and delayed cuts at each spinal level is recommended to address both fast and slow CSF leaks. CT myelography is most often used in the setting of a patient who has failed epidural blood patch and requires either surgical repair or fibrin glue injection. Magnetic resonance (MR) myelography is a growing cutting-edge technology that may serve as an alternative to CT myelography.
Treatment Treatment of low CSF-pressure headache whether secondary to a known cause or SIH, usually begins with conservative measures. These include bed rest, which is typically desired by patients with the most significant orthostatic headaches, coffee intake, hydration, and time. Most of these measures are based on long-term practices of treating post-LP headaches, and they will work in the majority of patients with low CSFpressure headaches. When dealing with SIH, some patients resolve in two weeks, while others continue to have headaches for several months or, rarely, even years [41]. Medications are also tried prior to procedural options, including analgesics for pain relief, caffeine and theophylline via intravenous infusions, and corticosteroids. The response to caffeine and theophylline is unpredictable, with some patients doing very well and others not responding. Corticosteroids provide relief in some patients, although the effects are transient. Epidural blood patch is currently the treatment of choice in patients who have not responded to conservative measures [52], and the mechanism of action is believed to be twofold. The first is volume replacement by compression of the dural sac that is believed to cause the immediate effect, and the second is sealing of the dural defect, which may be delayed from the first action. This may result in a waxing and waning clinical course, such as initial resolution of symptoms,
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followed by recurrence in 24 to 48 hours, then followed by gradual improvement. A previous failure of epidural blood patch should not preclude a repeat, should that be necessary, as many patients require several epidural blood patches to achieve freedom from symptoms. Epidural blood patch has an efficacy of only 30 % in SIH, but it is significantly higher in post-LP headache, at 90 % following first attempt [53, 54]. One of the reasons for this variance is that the target site for the epidural blood patch is typically close to the site of the leak, and while the site of the leak is likely in the posterior dura in post-LP headache, it is postulated that the site of the CSF leak in SIH is at the nerve root sleeves or nerve root axilla. Another reason for the difference is what is called the dural defect in SIH, which is the idea that an unsupported arachnoid in a preexisting zone of attenuated dura loses its integrity, causing CSF to leak from one or more sites. The use of fibrin glue to repair the leak is a technique that has shown promise. Once the location of the CSF leak has been identified, surgery is effective. Other treatment options that have had less reliable results include intrathecal fluid injection, epidural saline infusion, intravenous saline infusions, epidural infusion of dextran, and the use of an abdominal binder. There are five major complications of spontaneous CSF leaks that the reader should be aware of, as almost all of them will require corrective action. The first is subdural hematoma. These vary in size, and can be small and asymptomatic or large, resulting in compression of the brain. In the case of very large subdural hematoma, surgical intervention is warranted [55, 56]. Cerebral venous thrombosis (CVT) is another potential complication. Fortunately, this is an uncommon occurrence, but a rapid change in headache characteristics should prompt further investigation. CVT is typically treated with anticoagulation. The third is rebound intracranial hypertension, which is typically seen following successful treatment by epidural blood patch or surgery [57]. Another complication is bibrachial amyotrophy, where the patient presents clinically with weakness and atrophy of a few sequential myotomal distributions of the upper extremities. This is associated with mild asymmetry similar to what is seen in motor neuron disease [58], and is associated with extra-arachnoid fluid collection in the ventral aspect of the spinal cord, primarily in the cervical and thoracic regions, although it can extend to the lumbar region as well [13••]. Finally, superficial siderosis is a rare complication, although it has been described in association with spinal CSF leaks [59, 60]. This is characterized by extra-arachnoid fluid collections similar to those seen in bibrachial amyotrophy involving the ventral spinal cord.
Conclusions While headache associated with low CSF pressure is not rare, the diagnosis can be missed, especially in the case of
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spontaneous CSF leak where there is no history of dural puncture or significant trauma. The literature supports the theory that patients with an underlying connective tissue disorder may be at increased risk of developing a spontaneous CSF leak. Aside from the characteristic clinical presentation, which can vary somewhat, there are also several imaging modalities as well as LP to assist with diagnosis. Treatment options range from conservative to surgical repair. The natural course of this disorder in the majority of patients is spontaneous resolution, although the timeline to resolution is variable. Major complications are possible in conjunction with CSF leaks and, less commonly, following successful treatment. Compliance with Ethics Guidelines Conflict of Interest Dr. Roderick C. Spears declares no potential conflict of interest relevant to this article. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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