INTRODUCTION — The production, absorption, and flow of cerebrospinal fluid (CSF) play key roles in the dynamics of intracranial pressure. Alterations in CSF pressure can lead to neurologic symptoms, the most common being headache.

This topic will discuss the pathophysiology, epidemiology, clinical features, and diagnosis of headache attributed to spontaneous intracranial hypotension. Treatment is discussed separately. (See "Spontaneous intracranial hypotension: Treatment and prognosis".)

Post-lumbar puncture headache is reviewed elsewhere. (See "Post dural puncture headache".)

TERMINOLOGY — Spontaneous intracranial hypotension is being recognized with increasing frequency. Orthostatic headache, low cerebrospinal fluid (CSF) pressure, and diffuse meningeal enhancement on brain magnetic resonance imaging (MRI) are the major features of the classic syndrome. However, some cases have nonorthostatic headache, normal CSF pressure, or no evidence of diffuse meningeal enhancement [1].

Our understanding of spontaneous intracranial hypotension is still evolving, and historically a number of other terms have been used to describe it:

●Spontaneous (or idiopathic) low CSF pressure headache

●Low CSF volume headache

●Hypoliquorrhoeic headache

●Aliquorrhea

●CSF leak headache

●CSF hypovolemia

●CSF volume depletion

PATHOPHYSIOLOGY — In the intact craniospinal vault, the brain is supported by the cerebrospinal fluid (CSF), such that a brain weight of 1500 g in air is only 48 g in CSF [2]. As the CSF pressure decreases, there is a reduction in the buoyancy of the brain's supportive cushion. As a result, the brain "sags" in the cranial cavity, causing traction on the anchoring and supporting structures of the brain [3-6].

Most often, the headaches associated with low CSF pressure are orthostatic and occur after lumbar puncture, but similar headaches occur with spontaneous low CSF pressure due to spinal CSF leaks and with CSF shunt overdrainage. In addition, trauma, surgery, and other medical conditions have been associated with spontaneous intracranial hypotension [7].

Cause of headache — Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging veins, is thought to cause headache and some of the associated symptoms of spontaneous intracranial hypotension [5]. In the upright position this traction is exaggerated, hence the postural component of the headache. Secondary vasodilation of the cerebral vessels to compensate for the low CSF pressure may contribute to the vascular component of the headache by increasing brain volume [4]. Because jugular venous compression increases headache severity, it seems likely that venodilation is a contributing factor to the headache.

CSF hypovolemia, rather than CSF hypotension per se, has been proposed as the underlying cause of the headache syndrome [1], as patients with normal CSF pressure have been described who have clinical and radiographic features that are otherwise typical of orthostatic headache [1,8-10]. In this paradigm, the CSF pressures, clinical manifestations, and imaging abnormalities of the syndrome are thought to be variables dependent on CSF volume [11,12]. Some authors [13] have therefore advocated the name "CSF hypovolemia syndrome" for the constellation of symptoms associated with CSF leakage.

An alternative hypothesis is that spinal loss of CSF results in an increased compliance at the caudal end of the spinal CSF space, and the abnormal distribution of craniospinal elasticity causes the headache syndrome [14]. This explanation is compatible with the observation that spinal sites of CSF leakage commonly produce orthostatic headache, whereas cranial sites of CSF leakage (eg, seen with spontaneous CSF rhinorrhea or CSF otorrhea) rarely if ever do so. (See 'CSF leak' below.)

Cause of low CSF pressure — In 1891, Quincke introduced the lumbar puncture (LP) [15], and in 1898 Bier suffered and was the first to report post-LP headache [16]. He proposed that ongoing leakage of CSF through the dural puncture site was the cause of the headache. This belief is still held today. It is thought that leakage of CSF through the dural rent made by the LP needle exceeds the rate of CSF production, resulting in low CSF volume and pressure [17]. (See "Post dural puncture headache", section on 'Pathophysiology'.)

The clinical syndrome of headache attributed to spontaneous intracranial hypotension has been recognized for many years. The syndrome was first proposed in 1938 by Schaltenbrand [18,19], who termed it aliquorrhea, and described a headache syndrome virtually identical to that following LP. He proposed three possible mechanisms (decreased CSF production by the choroid plexus, increased CSF absorption, and CSF leakage through small tears) to explain the symptoms.

CSF leak — The prevailing theory for the etiology of spontaneous intracranial hypotension is that of CSF leakage located in the spine, which may occur in the context of disruption of the meninges [20]. An underlying connective tissue disorder may result in dural weakness and play a role in the development of spontaneous low CSF pressure, as suggested by studies reporting abnormal connective tissue abnormalities in patients with spontaneous CSF leaks [21,22] and/or deficient fibrillin, elastin, or both in dermal fibroblast cultures from such patients [23]. Meningeal diverticula, often seen in patients with CSF leaks, may be related to this connective tissue problem [24], and meningeal diverticula have been described in patients with Marfan syndrome [22].

A potential contributing factor to the development of spontaneous low CSF pressure is that of minor trauma or an inciting event, including a fall, a sudden twist or stretch, sexual intercourse or orgasm, a sudden sneeze, sports activity, or "trivial trauma" [25]. These relatively minor events may cause rupture of spinal epidural cysts (formed during fetal development) or perineural (Tarlov) cysts, or may cause a tear in a dural nerve sheath [20] with resultant cryptic CSF leakage.

In addition, degenerative disc disease, osseous spurs, and microspurs may lead to spontaneous intracranial hypotension by causing dural tears [26-30]. Another uncommon cause is the spontaneous development of a spinal CSF venous fistula, which enables CSF to drain from the subarachnoid space directly into adjacent spinal epidural veins in the absence of a dural defect [31,32]. This subtype has been increasingly recognized with the advancement of diagnostic radiology tools.

●Location – The location of CSF leaks associated with spontaneous intracranial hypotension is almost exclusively spinal; most occur at the thoracic or cervicothoracic junction. Few, if any, cases result from CSF leaks at the skull base. As an example, one series evaluated 273 patients with spontaneous intracranial hypotension, and none had evidence of a cranial CSF leak [33].

Although less common, in contrast to spinal leaks, some cases of spontaneous CSF leaks at the skull base (ie, into the petrous or ethmoidal regions, or through the cribriform plate, and typically associated with overt CSF rhinorrhea or otorrhea) may result from sustained intracranial hypertension as occurs in idiopathic intracranial hypertension [34-36]. (See "Idiopathic intracranial hypertension (pseudotumor cerebri): Epidemiology and pathogenesis" and "Idiopathic intracranial hypertension (pseudotumor cerebri): Clinical features and diagnosis".)

●Classification – Advances in the understanding of the anatomy of spontaneous spinal CSF leaks have led to the development of a comprehensive classification system. This system, based upon a review of 568 patients with spontaneous intracranial hypotension, classifies CSF leaks based on their underlying cause (dural tear, meningeal diverticulum, or CSF-venous fistula) and the presence or absence of extradural CSF on spinal imaging [37].

•Type 1 CSF leaks resulted from a dural tear and accounted for 27 percent of cases; nearly all were associated with an extradural CSF collection. Type 1a were ventral CSF leaks (96 percent) and type 1b were posterolateral CSF leaks (4 percent).

•Type 2 CSF leaks resulted from meningeal diverticula and accounted for 42 percent of leaks; an extradural CSF collection was present in 22 percent of patients with type 2 leaks. Type 2a represented simple diverticula (91 percent) and type 2b complex meningeal diverticula/dural ectasia (9 percent).

•Type 3 CSF leaks resulted from direct CSF-venous fistulas and accounted for 2.5 percent of cases; type 3 leaks were not associated with extradural CSF collections.

•Type 4 CSF leaks were of indeterminate source and accounted for 29 percent of cases; extradural CSF collections were present in 52 percent of patients with type 4 leaks.

Low venous pressure — An alternative hypothesis postulates that spontaneous intracranial hypotension results primarily from the lowering of venous pressure within the inferior vena cava system, amplified by the displacement of blood toward the heart that occurs due to the activation of leg muscles during standing and walking [38]. The lower pressure in the inferior vena cava leads to epidural venous hypotension and outflow of CSF along the spinal cavity, and in some cases precipitates actual CSF leaks from existing radicular meningeal diverticula or cysts. In this paradigm, dural tears are not the cause of the condition but instead are a result of the low epidural pressure. Blood patching at the epidural lumbar space used to treat the condition does not work by sealing CSF leaks, but instead is effective because it disconnects the low-pressure epidural lumbar venous network, which drains to the inferior vena cava, and diverts venous return to the epidural thoracic and cervical venous network, which drains to the superior vena cava.

This hypothesis has been challenged by experts who dispute a number of its assumptions regarding the anatomic and pathophysiologic characteristics of the spinal epidural veins [39]. In addition, the skeptics point out radiologic evidence that epidural veins are distended and the epidural sac is collapsed in patients with spontaneous intracranial hypotension prior to treatment, and that the epidural veins and dural sac return to normal proportions after treatment with blood patch [40]. These pre-treatment observations are best explained by CSF hypotension with dural sac collapse and expansion of the extradural space [39].

EPIDEMIOLOGY — There are few data regarding the incidence of spontaneous intracranial hypotension. The estimated annual incidence is 5 per 100,000 [41]. In a systematic review from 2021, the following observations were made [42]:

●The mean age of patients was 43 years with a range from 2 to 88 years of age

●The proportion of female individuals was 63 percent

Although data are limited, possible risk factors for spontaneous intracranial hypotension include connective tissue abnormalities, spinal pathologies, and bariatric surgery [42-44]. (See 'CSF leak' above.)

CLINICAL FEATURES — Postural headache is usually but not always the major manifestation of spontaneous intracranial hypotension. Occasionally patients report no headache, typically when other symptoms of low cerebrospinal fluid (CSF) pressure are predominant [41,42]. (See 'Associated symptoms and complications' below.)

The neurologic examination is often normal in patients with spontaneous intracranial hypotension [45]. However, various neurologic symptoms and signs may be present. (See 'Associated symptoms and complications' below.)

Headache — Headache attributed to spontaneous intracranial hypotension may be of sudden or gradual onset. The headache ordinarily develops within two hours, and in most cases within 15 minutes, of sitting or standing [46]. Rarely, it starts as a thunderclap headache [24]. (See "Overview of thunderclap headache".)

The headache with this syndrome is often described as throbbing or dull pain that may be generalized or focal. The headache severity is widely variable and ranges from mild to incapacitating [41]. Frontal pain is reported by patients as often as occipital and diffuse pain [25,42].

Headache relief is typically obtained with recumbency, usually within minutes. In rare cases associated with an asymmetric cervical CSF leak, headache relief occurs only with lying on one side of the body [47]. The headache is seldom relieved with analgesics. Exacerbating factors include erect posture, head movement, coughing, straining, sneezing, jugular venous compression, and high altitude [48].

While headache attributed to spontaneous intracranial hypotension is characteristically orthostatic, other patterns can occur [49]:

●During the course of the illness, the orthostatic features may disappear, and a chronic daily headache may develop [12,24]. On occasion, the postural component may not be present at all.

●Paradoxical headache, worse with recumbency and better with the upright position, has been reported in rare patients with spontaneous low CSF pressure [50,51].

●In some cases, the headache is more prominent later in the day and lacks clear orthostatic features; the headache is usually absent in the morning and begins in late morning or early afternoon, increasing in severity as more time is spent upright [52]. This pattern may be caused by a low-volume ("slow-flow") CSF leak or leaks that have slowed due to chronicity or treatment.

●Patients with intermittent CSF leaks may present with intermittent headaches with headache-free intervals of varying duration.

●In other cases, the headache can mimic a primary headache syndrome, such as primary cough headache [53] or primary exertional headache [54]. These primary headache syndromes are discussed separately. (See "Primary cough headache" and "Exercise (exertional) headache".)

Headache attributed to spontaneous intracranial hypotension may resolve spontaneously within two weeks [45]. In some cases, it lasts months or years.

Associated symptoms and complications — In 1825, Magendie described vertigo and unsteadiness in a patient following the removal of CSF [55]. Today, the list of reported associated symptoms is varied and extensive [41,42]. In a systematic review including 32 articles and 1531 patients, the most common associated symptoms of spontaneous intracranial hypotension were [42]:

●Nausea or vomiting – 51 percent

●Neck pain or stiffness – 33 percent

●Tinnitus – 19 percent

●Dizziness – 14 percent

Other associated symptoms include the following [41,42]:

●Change in hearing (eg, hyperacusis, echoing, or tinnitus) [1,15,25]

●Photophobia

●Other visual disturbances (eg, blurred vision, diplopia, visual obscurations) [2]

●Vertigo

●Diaphoresis

●Anorexia

●Unsteadiness or staggering gait [17]

●Reduced level of consciousness

●Back pain

●Hiccups

●Dysgeusia [25]

Additional rare manifestations associated with the syndrome are probably due to distortion or compression of brain and/or spinal cord structures. These manifestations (and associated central nervous system structures) are as follows [56]:

●Subdural hematoma [57-60]

●Galactorrhea and hyperprolactinemia (pituitary stalk) [61]

●Ataxia (posterior fossa)

●Quadriparesis (brainstem and upper cervical spinal cord) [51]

●Cerebellar hemorrhage (cerebellar bridging veins) [51]

●Posterior circulation infarction (deformation of cerebral arteries) [62-64]

●Movement disorders including parkinsonism, tremor, chorea, and dystonia (deep midline structures) [65-67]

●Hypoactive behavior (pons and midbrain) [68]

●Decreased level of consciousness, stupor, and coma (diencephalon) [69-71]

●Cerebral venous sinus thrombosis [72]

Except for hemorrhage and infarction, these manifestations are typically reversible with successful treatment of the CSF leak. The role of anticoagulation in cerebral venous sinus thrombosis treatment in the setting of spontaneous intracranial hypotension remains uncertain and potential benefits must be weighed against risks of hemorrhage, particularly for patients with subdural fluid collections.

Several reports have noted the development of superficial siderosis, characterized by hemosiderin deposition in the leptomeninges and subpial layer, often years after the onset of spontaneous intracranial hypotension [73-77]. The proposed mechanism is recurrent hemorrhage from friable vessels at the site of the CSF spinal leak or from cerebellar bridging veins that are stretched due to brain sagging. (See "Superficial siderosis".)

In rare cases, spontaneous intracranial hypotension has been associated with alterations of cerebrovascular tone, including:

●Reversible posterior leukoencephalopathy syndrome (also known as posterior reversible encephalopathy syndrome or PRES) [78,79] (see "Reversible posterior leukoencephalopathy syndrome")

●Reversible cerebral vasoconstriction syndromes [80] (see "Reversible cerebral vasoconstriction syndrome")

Subtle cognitive deficits may be associated with the spontaneous intracranial hypotension and are typically reversible with successful treatment of the CSF leak [41]. Frank dementia is rare, but cases of reversible frontotemporal dementia attributed to low CSF pressure have been reported [81,82]. Another report described eight patients with "frontotemporal brain sagging syndrome" (FBSS) who presented with progressive behavioral symptoms and cognitive dysfunction suggestive of behavioral variant frontotemporal dementia [83]. Atypical clinical features included headache and daytime somnolence. Magnetic resonance imaging (MRI) in all cases revealed sagging of the frontal and temporal lobes with downward displacement of the cerebellar tonsils, swelling of the midbrain, flattening of the ventral pons, and effacement of the basal cisterns. Two patients had pachymeningeal enhancement. Treatments directed at intracranial hypotension led to unsustained improvement in a few patients. Frontotemporal dementia is discussed separately. (See "Frontotemporal dementia: Clinical features and diagnosis".)

EVALUATION AND DIAGNOSIS — The diagnosis of spontaneous intracranial hypotension should be considered in patients who present with positional orthostatic headache, with or without associated symptoms, perhaps in the setting of minor trauma, and in the absence of a history of dural puncture or other cause of cerebrospinal fluid (CSF) fistula [41]. Headache caused by low CSF pressure following a lumbar puncture rarely creates a clinical dilemma.

Confirmation of the diagnosis requires evidence of low CSF pressure, most often by magnetic resonance imaging (MRI; eg, pachymeningeal enhancement) or by radioisotope cisternography, and/or evidence of a CSF leak on other neuroimaging studies, mainly computed tomographic (CT) myelography.

For patients with suspected spontaneous intracranial hypotension, we recommend brain MRI with gadolinium and MRI of the spine without gadolinium to assess for the typical imaging features of the syndrome (algorithm 1), which are diffuse pachymeningeal enhancement (image 1), "sagging" of the brain, tonsillar descent, posterior fossa crowding (image 2), and dilated cervical epidural veins. (See 'Brain MRI' below and 'Spine MRI' below.)

Where available, radioisotope cisternography is usually obtained as the next step if a CSF leak is suspected and MRI is normal or nondiagnostic. (See 'Radioisotope cisternography' below.)

Once the diagnosis is confirmed, the need for further evaluation to confirm the exact site of the CSF leak is driven by the response to therapy. Patients who fail adequate trials of conservative therapy and repeated epidural blood patch treatments, the mainstay of therapy, may require definitive localization of the CSF leak or leaks in order to have surgical repair. This is usually accomplished with CT myelography (see 'CT myelography' below), though magnetic resonance (MR) myelography (see 'MR myelography' below) is an alternative method. The localization of rapid (ie, high-flow) CSF leaks may require dynamic CT myelography (see 'Dynamic CT myelography' below) or digital subtraction myelography (see 'Digital subtraction myelography' below).

Diagnostic criteria — Diagnostic criteria for headache attributed to spontaneous intracranial hypotension, as delineated by the International Classification of Headache Disorders, 3^rd edition (ICHD-3), are as follows [84]:

●(A) Any headache fulfilling criterion C

●(B) Either or both of the following:

•Low CSF pressure (<60 mmH₂0)

•Evidence of CSF leakage on imaging

●(C) Headache has developed in temporal relation to the low CSF pressure or CSF leakage, or has led to its discovery

●(D) Not better accounted for by another ICHD-3 diagnosis

Neuroimaging — Brain MRI is the preferred modality for confirming the diagnosis of spontaneous intracranial hypotension. Spine MRI, radioisotope cisternography, and CT myelography can also be useful, particularly when brain MRI is nondiagnostic. However, neuroimaging studies are generally not done in patients with post-lumbar puncture headache, where the diagnosis is more obvious.

The utility of head CT for confirming the diagnosis is limited, as head CT is often normal in patients with spontaneous intracranial hypotension. However, head CT may suggest the diagnosis by demonstrating subdural fluid collections, slit-shaped ventricles, tight basal cisterns, scant CSF over the cortex, or increased tentorial enhancement [41].

Brain MRI — The advent of magnetic resonance imaging (MRI) has greatly improved the diagnosis of spontaneous intracranial hypotension. While brain and/or spine MRI is abnormal in most patients, a systematic review estimated that brain MRI remains normal in up to 20 percent of patients with spontaneous intracranial hypotension [41,42]. A subsequent report evaluated 18 patients with spontaneous intracranial hypotension and found that the sensitivities of brain and spine MRI were 83 and 94 percent, respectively [40].

●The most common abnormality on brain MRI is diffuse meningeal enhancement (DME), found in nearly 75 percent of patients with intracranial hypotension (image 1) [8,42].

●Other abnormal features on brain MRI variously found in approximately one third up to one half of patients include the following [42]:

•Subdural hematomas or hygromas, presumably from rupture of the bridging veins as the CSF volume decreases [55,85]

•"Sagging" of the brain, with cerebellar tonsillar herniation and descent of the brainstem mimicking a Chiari I malformation (image 2) [86]

•Engorgement of cerebral venous sinuses [87]

•Pituitary enlargement [88,89], flattening of the optic chiasm, and increased anteroposterior diameter of the brainstem

•Decrease in the size of cisterns and ventricles

The acronym SEEPS (for Subdural fluid collections, Enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain) recalls the major features of spontaneous intracranial hypotension on brain MRI [41].

Meningeal enhancement involves the pachymeninges and spares the leptomeninges, without abnormal enhancement in the depth of the cortical sulci or around the brainstem (image 1) [8,90-92]. It is also contiguous (without skip areas), non-nodular, and involves both supratentorial and infratentorial compartments. The enhancement is often thick and obvious, but sometimes can be quite thin. Diffuse meningeal enhancement (DME) may improve or resolve with resolution of the headache.

DME is believed to be secondary to vascular dilatation. According to the Monro-Kellie doctrine [93], any decrease in CSF volume must be compensated given the noncompressible nature of the skull. As a result, loss of CSF volume results in an increase in intracranial blood volume, and venous engorgement results in a greater concentration of gadolinium in the dural vasculature and interstitial fluid of the dura.

A minority of patients with spontaneous intracranial hypotension may present with swelling of the upper brainstem and diencephalon and little or no DME or subdural fluid collections on MRI [94]. The upper brainstem swelling is hypothesized to be a manifestation of venous stagnation caused by downward stretching of the vein of Galen, which results in a functional stenosis where the vein of Galen joins the straight sinus. This results in a narrowing of the midbrain-pons angle which has been associated with a poorer response to spontaneous intracranial hypotension treatment [95] and can be used as an indicator of spinal CSF leakage severity [96].

Spine MRI — Spinal MRI may be helpful both for confirming the diagnosis and for identifying the exact location of the CSF leakage. Such studies may reveal [97,98]:

●Extra-meningeal fluid collections

●Collapse of the dural sac and engorgement of the epidural venous plexus

●Meningeal diverticula

●Extradural extravasation of fluid

In a series of 10 female patients who had characteristic orthostatic headache without a previous history of dural tear, spinal MRI revealed dilated cervical epidural veins [13]. The authors concluded that this finding is an indicator of CSF hypovolemia and can be used to differentiate spontaneous low CSF pressure from the other causes of diffuse meningeal enhancement.

Subtraction MRI employs rapid postprocessing image analysis of standard T2 and T1 MRI sequences in order to delineate the dural sac of the spinal cord and distinguish between fluid and fat. In a report of 17 patients with spontaneous intracranial hypotension, subtraction MRI of the spinal cord identified the epidural CSF fluid collection in all patients, although the site of the CSF leak was not detected [99]. Additional studies are needed to determine the sensitivity and specificity of this method.

Radioisotope cisternography — Radioisotope cisternography is not widely available but is particularly useful for confirming a CSF leak in the setting of spontaneous intracranial hypotension [100]. At centers with experience in its performance and interpretation, radioisotope cisternography is usually obtained as the next step if a CSF leak is suspected and MRI is normal or nondiagnostic (algorithm 1). Radioisotope cisternography is not well-suited for localizing the leak, but in a minority of patients may reveal direct evidence of the exact site of the CSF leak in the form of paradural extravasation of radioisotope [100,101].

The procedure involves intrathecal injection, via lumbar puncture, of a radioisotope (indium-111 DTPA) [102]. The dynamic flow of the isotope is followed by scanning at predetermined intervals for 24 or 48 hours. Since a lumbar puncture is required as part of the procedure (see 'Lumbar puncture' below), opening CSF pressure is measured, and CSF is sent for analysis at the same time. Placement of numbered cotton pledgets in the nose for subsequent detection of radioactivity aids in detection and localization of CSF leakage through the paranasal sinuses.

Normal CSF flow involves cephalad migration from the site of injection to the cerebral convexities and the sylvian fissures [4], and, therefore, the most common cisternographic abnormality in CSF leaks is the absence or paucity of activity over the cerebral convexities (image 3), which provides reliable though indirect evidence of the presence of a leak [103-105]. Other findings suggestive of a CSF leak, though not as reliable, include early accumulation of radioisotope within the bladder and kidneys, leakage of isotope outside of the normal confines of the subarachnoid space, and early soft tissue uptake of radioisotope. In contrast, the presence of radioactivity over the cerebral convexities at 24 hours argues against an active CSF leak [102].

In a minority of subjects with spontaneous intracranial hypotension, radioisotope cisternography reveals direct evidence of the exact cite of the CSF leak in the form of paradural extravasation of radioisotope [100,101].

In a small retrospective study of patients with spontaneous CSF leaks, the diagnosis of intracranial hypotension was supported in all 10 patients who had radionucleotide cisternography, which showed early bladder accumulation of the nucleotide and reduced activity over the cerebral hemispheres, consistent with rapid uptake of the tracer in the bloodstream [106]. In addition, the location of the leaks was identified in 7 of the 10 patients with this method.

Iatrogenic CSF leak from the lumbar puncture is a potential complication of radioisotope cisternography [107].

CT myelography — CT myelography is the best test to identify the exact site of the CSF leak caused by a dural defect [102]. CT myelography is most commonly used in order to localize the level of the spinal leak when treatment beyond epidural blood patch (such as surgery or fibrin glue injection) is contemplated. (See "Spontaneous intracranial hypotension: Treatment and prognosis".)

Both early and delayed cuts should be obtained at each spinal level, since CSF leaks may be rapid or slow. In cases where radioisotope cisternography or spinal MRI has identified the approximate level of the leak, focused CT cuts can be used to locate the source more precisely.

Despite the utility of CT myelography for determining the site of CSF leak, the results can occasionally be misleading. In particular, retrospinal CSF collections at the C1-C2 level and CSF extravasation into surrounding tissues at the cervicothoracic junction may be false localizing signs [108,109].

Dynamic CT myelography — Dynamic CT myelography, where images are obtained during intrathecal contrast injection while the patient is in the CT scanner, has improved temporal and spatial resolution compared with routine CT myelography, where intrathecal contrast is given prior to moving the patient to the CT scanner [110]. Thus, dynamic CT myelography is better suited than routine CT myelography to detecting rapid or high-flow CSF leaks [111]. In several cases when routine CT myelography showed no evidence of a CSF leak through a dural defect, positive-pressure dynamic CT myelography has revealed direct CSF flow through a spinal venous fistula as the cause of spontaneous intracranial hypotension [31].

The temporal resolution of digital subtraction myelography (see 'Digital subtraction myelography' below) may be even better than that of dynamic CT myelography.

MR myelography — Evidence suggests that noncontrast MR myelography using heavily T2-weighted sequences may be an alternative to CT myelography for detecting the level of CSF leaks [42,112,113].

MR myelography with intrathecal gadolinium can sometimes detect the site of a slow-flow CSF spinal leak [102,114,115]. This method is generally reserved for patients with debilitating symptoms of spontaneous intracranial hypotension when the site of the CSF leak has not been identified by CT myelography and other techniques.

Digital subtraction myelography — Small retrospective reports suggest that digital subtraction myelography using intrathecal injection of contrast material is useful to detect the site of spinal dural tears in select patients with rapid CSF leaks [42,116-118]. The temporal resolution of CT and MR myelography can be inadequate in the setting of rapid CSF leaks because the contrast can spread over many spinal levels during the time needed to obtain the CT or MRI images, obscuring the exact site of the dural defect [118]. Such rapid CSF leaks typically appear on CT and MRI as longitudinally extensive extradural fluid collections that are ventral to the spinal cord.

The superior temporal resolution of digital subtraction myelography may also be useful for the detection of direct spinal venous fistulae, which have been implicated as the cause of spontaneous intracranial hypotension in cases where routine CT myelography and MRI myelography failed to identify a dural defect [31,32].

Although data are limited, the presence or absence of spinal longitudinal extradural CSF collection on MRI may be useful to guide patient positioning (prone or lateral decubitus) for digital subtraction myelography for patients with spontaneous intracranial hypotension that is refractory to initial epidural blood patch [119]. For patients with spinal longitudinal extradural collections, prone positioning may assist in localizing the site of dural tears; in those without spinal longitudinal extradural CSF collections, decubitus positioning may improve detection of a CSF-venous fistula, which is relatively common in this population. However this approach is based on a retrospective review of only 31 patients [119], and further experience is needed before it can be widely recommended.

Lumbar puncture — A lumbar puncture (LP) can document low CSF pressure in suspected cases of spontaneous intracranial hypotension, and may be diagnostically useful when MRI is not available or is not tolerated. However, LP is generally not necessary in cases where MRI is consistent with the diagnosis of spontaneous intracranial hypotension. There is also concern that dural puncture from the procedure could potentially worsen the low CSF pressure and exacerbate the syndrome.

The opening pressure with LP in patients with spontaneous intracranial hypotension usually ranges from 0 to 70 millimeters of water (mmH₂O) [3], whereas normal opening pressure is generally considered to be 60 to 200 mmH₂O in adults and children; opening pressures up to 250 mmH₂O may be normal in obese people. (See "Cerebrospinal fluid: Physiology and utility of an examination in disease states", section on 'Physiology of CSF formation and flow'.)

In a review of 738 patients including 21 studies, the opening pressure was low in 67 percent but normal in 32 percent of patients [42]. Normal opening pressure in some cases of proven spontaneous intracranial hypotension may occur if the measurement is made after a period of recumbency, if the CSF leak is intermittent, or if the CSF leak is chronic [12,120]. Even within the same patient, the CSF pressure may vary from LP to LP. For greater accuracy, CSF pressure should be measured with the patient in the lateral decubitus position if an LP is performed. To ascertain correct placement of the spinal needle, CSF flow should be observed either spontaneously, with gentle aspiration, or with Valsalva maneuver [15]. (See "Lumbar puncture: Technique, indications, contraindications, and complications in adults".)

In patients with spontaneous intracranial hypotension, LPs are often difficult. Repeated attempts may be needed to obtain CSF, and traumatic blood-tinged fluid may result. In addition, so-called "dry taps" may be encountered, requiring cisternal taps to collect the fluid. In rare instances, the CSF pressure is negative (below that of atmospheric pressure), and a sucking noise may be heard when the stylet is removed from the LP needle.

The CSF is typically clear and colorless. Common CSF abnormalities include a moderate lymphocytic pleocytosis (up to 50 cells/mm³), the presence of red blood cells, and elevated protein (commonly up to 100 mg/dL) [8]. The CSF pleocytosis likely reflects a reactive phenomenon secondary to hydrostatic pressure changes [45]. The elevated protein may be related to lowered CSF pressure leading to disruption of normal hydrostatic and oncotic pressure across the venous sinus and arachnoid villi, resulting in the passage of serum protein into the CSF [45].

CSF cytology and microbiology is always normal and CSF glucose is never low [97].

DIFFERENTIAL DIAGNOSIS — Patients who have cerebrospinal fluid (CSF) shunts placed for various neurosurgical indications may develop a syndrome identical to that of spontaneous intracranial hypotension, probably secondary to overdrainage (over shunting) of CSF [8].

Orthostatic headache in the absence of CSF leak may also be a manifestation of the postural tachycardia syndrome or orthostatic intolerance [121]. (See "Postural tachycardia syndrome".)

One case report described spontaneous orthostatic headache and a "dry tap" at lumbar puncture that was attributed to an intradural myxopapillary ependymoma [122].

Misdiagnosis — The syndrome of spontaneous intracranial hypotension has been under-recognized, in part because headache in general is a common ailment, and because patients with headache attributed to spontaneous intracranial hypotension typically present with a normal neurologic examination. The diagnosis was often missed prior to the advancement of magnetic resonance imaging (MRI) and the specific MRI findings associated with the syndrome. Even in the modern era of MRI availability, misdiagnosis is common [123].

Inappropriate and unnecessary clinical investigations may result if the diagnosis of spontaneous intracranial hypotension is not considered. As an example, before diffuse meningeal enhancement on brain MRI was a recognized feature of spontaneous intracranial hypotension, patients with this finding were often subjected to extensive testing to rule out other causes such as meningeal carcinomatosis, meningitis, subarachnoid hemorrhage, neuroborreliosis, and neurosarcoidosis. (See 'Brain MRI' above.)

SUMMARY AND RECOMMENDATIONS

●The classic features of spontaneous intracranial hypotension are orthostatic headache, low cerebrospinal fluid (CSF) pressure, and diffuse meningeal enhancement on brain magnetic resonance imaging (MRI). (See 'Introduction' above and 'Clinical features' above.)

●The prevailing etiology of spontaneous intracranial hypotension is CSF leakage at the level of the spinal cord, which may occur in the context of rupture of the meningeal membrane. An alternative hypothesis is that low CSF pressure is caused by epidural venous hypotension from the lowering of venous pressure within the inferior vena cava system. Most CSF leaks occur at the thoracic or cervicothoracic junction. An underlying connective tissue disorder may play a role in the development of CSF leaks. Other potential contributing factors are minor trauma, degenerative disc disease, and osseous spurs. (See 'Pathophysiology' above.)

●Traction on pain-sensitive intracranial and meningeal structures, particularly sensory nerves and bridging veins, is thought to cause headache and some of the associated symptoms. (See 'Pathophysiology' above.)

●The estimated annual incidence of spontaneous intracranial hypotension is 5 per 100,000, with a peak incidence around age 40 and a female to male ratio of 2:1. (See 'Epidemiology' above.)

●Headache attributed to spontaneous intracranial hypotension may be sudden or gradual in onset, and severity is widely variable. The headache is typically relieved with recumbency and exacerbated with upright posture. Other headache patterns have also been reported with this syndrome. Commonly associated symptoms are neck pain or stiffness, nausea and vomiting, change in hearing, and photophobia. There is a varied and extensive list of additional associated symptoms. (See 'Clinical features' above and 'Headache' above and 'Associated symptoms and complications' above.)

●Some rare but serious symptoms (eg, altered level of consciousness, parkinsonism) associated with the syndrome are probably caused by distortion or compression of brain and/or spinal cord structures. (See 'Associated symptoms and complications' above.)

●The diagnosis of spontaneous intracranial hypotension should be considered in patients who present with positional orthostatic headache, with or without associated symptoms, perhaps in the setting of minor trauma, and in the absence of a history of dural puncture or other cause of CSF fistula. Confirmation of the diagnosis requires evidence of low CSF pressure by MRI or lumbar puncture and/or evidence of a CSF leak on computed tomography (CT) myelography or radioisotope cisternography. (See 'Evaluation and diagnosis' above and 'Diagnostic criteria' above.)

●For patients with suspected spontaneous intracranial hypotension, we recommend brain MRI with gadolinium and spine MRI without gadolinium. Typical features on brain MRI include diffuse meningeal enhancement (image 1), subdural hematomas or hygromas, sagging of the brain (image 2), engorgement of cerebral venous sinuses, and pituitary enlargement. Brain MRI remains normal in up to 20 percent of patients with spontaneous intracranial hypotension. (See 'Brain MRI' above and 'Spine MRI' above.)

●Patients who have CSF shunts in place may develop a syndrome identical to that of spontaneous intracranial hypotension, probably secondary to overdrainage (over shunting) of CSF. (See 'Differential diagnosis' above.)

●Treatment of spontaneous intracranial hypotension is discussed separately. (See "Spontaneous intracranial hypotension: Treatment and prognosis".)