Spontaneous intracranial hypotension

Intracranial hypotension, also known as craniospinal hypotension is a clinical entity that results from a CSF leak usually from the spine from a variety of underlying causes. It usually, but not invariably, presents clinically with orthostatic headaches. Diagnosis of the leak and treatment are challenging.

Terminology

As understanding of CSF dynamics and the pathophysiology of CSF leaks has evolved, the terminology has become somewhat confusing.

Intracranial hypotension can broadly be divided into:

1. primary: usually referred to as spontaneous intracranial hypotension

2. secondary: iatrogenic (lumbar puncture or surgery), over-shunting due to diversion devices, or traumatic

Importantly, intracranial hypotension should not be thought of as being synonymous with all causes of CSF leak. When a CSF leak occurs from the base of the skull (e.g. rhinorrhoea or otorrhoea) then presentation is not typically with clinical or imaging features of intracranial hypotension due to the normal differences in CSF pressure in the neuraxis (see hydrostatic indifference point) ^25,26.

Similarly, middle cranial fossa meningoceles seen in patients with underlying idiopathic intracranial hypertension do not usually manifest with clinical or imaging features of intracranial hypotension ^26,29.

Epidemiology

Spontaneous intracranial hypotension is typically encountered in middle age (30-50 years of age) and has a predilection for women (F:M = 2:1). Of interest, this is a similar demographic to idiopathic intracranial hypertension, which is believed to be an unrecognised predisposing factor.

Epidemiology of secondary intracranial hypotension is variable and matches that of the underlying cause.

Clinical presentation

The condition often presents as a postural/orthostatic headache which is relieved by lying in a recumbent position, usually within 15-30 minutes ¹². This is, however, not always the case. Some patients have headaches that are not relieved by lying down, others have headaches that develop slowly during the course of the day (“second half of the day” headaches) ²⁶. Other symptoms include nausea, vomiting, neck pain, visual and hearing disturbances including tinnitus, and vertigo ^17,26.

Occasionally, presentation is more sinister, with frontotemporal brain sagging syndrome (FBSS). In this phenotype, patients present with a progressive cognitive impairment mimicking behavioural variant frontotemporal lobar degeneration (dementia), may have decreased level of consciousness and coma, and may have parkinsonism ^3,31. Compulsive repetitive flexion (at the waist) with breath-holding may be a useful clinical sign to differentiate these patients from those with behavioural variant frontotemporal lobar degeneration ³¹.

Another uncommon manifestation, and potentially masking the underlying presence of hypotension is the development of cerebral venous thrombosis, said to occur in approximately 2% of cases of intracranial hypotension ²³.

Diagnosis

Historically, intracranial hypotension was formally diagnosed by demonstrating an opening pressure on lumbar puncture of less than <6 cm H₂O ¹⁷. Note that if done fluoroscopically, lumbar puncture should be performed in a lateral position to allow for accurate measurement of pressure.

More recent studies have shown that althouhgalthough low CSF opening pressure is common, not all patients have very low pressures. A significant proportion have pressures between 6 - 20-20 cm H₂O whilst a smaller proportion have normal CSF pressures ²⁶.

Pathology

Intracranial hypotensionmost commonly results from a CSF leak somewhere along the neuraxis, usually below the hydrostatic indifference point and leads to alterations in the equilibrium between the volumes of intracranial blood, CSF, and brain tissue (Monro-Kellie hypothesis). A decrease in CSF volume leads to compensatory dilatation of the vascular spaces, mostly the venous side due to its higher compliance. 

Aetiology

Spontaneous intracranial hypotension is usually the result of a CSF leak in the spine.

Spontenaous Spontaneous leaks have been classified into 4four types ^27,28 and include multiple causes ^{9,12,13,25,26}:

• type 1: dural tear (most often ventral)

  • typically related to calcified thoracic disc protrusions

• type 2: ruptured meningeal diverticulum along the proximal nerve root

• type 3: CSF venous-venous fistula ^16,24,26

• type 4: distal nerve root sleeve leaks ²⁸

  • congenital focal absence of dura (nude nerve root): rare

Additionally, CSF leaks can be secondary trauma (e.g. penetrating injury) or iatrogenic (e.g. lumbar puncture, surgery).

Radiographic features

Imaging is crucial both for confirming the diagnosis of intracranial hypotension and identifying the location of the leak. The latter is discussed below in the "imaging strategy" section. 

CT

Described features of intracranial hypotension include:

• subdural collection

• acquired tonsillar ectopia

• dural venous sinus distention

• layer cake skull: diffuse layered calvarial hyperostosis seen in 14 - 32-32% of patients ^21,30

MRI

The most common qualitative finding is pachymeningeal thickening and enhancement followed by dural venous engorgement, tonsillar herniation, and subdural collection; however, these features are not always present, which is why quantitative findings are very helpful in making a more accurate diagnosis on MRI.

• qualitative signs

  • pachymeningeal enhancement (most common finding): becomes less prevalent over time after the onset of symptoms; hence, in patients with a chronic duration of symptoms in whom clinically the headache pattern also changes from orthostatic to atypical constant headache, the absence of dural enhancement may hinder the diagnosis of intracranial hypotension ¹⁵

  • increased venous blood volume

    • venous distension sign: rounding of the cross-section of the dural venous sinuses

    • prominence of inferior intercavernous sinuses is not a sensitive or specific finding; however, it is important to recognise that in cases of intracranial hypotension, should not be mistaken for a pituitary lesion ¹⁴

    • intracranial venous thrombosis is a well-recognised, albeit uncommon, complication and may involve the cortical veins and/or dural venous sinuses ¹⁹

  • enlargement of the pituitary gland

  • subdural effusions and eventual subdural haematomas

  • diffuse cerebral oedema ³

  • reduced CSF volume

    • sagging brainstem and acquired tonsillar ectopia

    • drooping splenium of the corpus callosum

    • decreased fluid within the optic nerve sheath ⁸

• quantitative signs

  • mamillopontine distance <5.5 mm ⁷

  • pontomesencephalic angle <50˚

  • interpeduncular angle <40.5° measured in the axial plane at or immediately below the level of the mammillary bodies ¹⁸ 

A useful mnemonic to remember the aforementioned features is SEEPS.

Imaging strategy

Identifying the site of CSF leakage can be challenging, especially in spontaneous cases, and embarking upon imaging can be daunting, as the leak can be located anywhere along the neuraxis (although usually in the spine) and leaks can vary dramatically in their rate ranging from large volume rapid leaks to slow leaks to intermittent/inapparent leaks or those where the connection is directly into the venous system (CSF-venous fistula) thich therefor have no pooling of CSF. As a result, no single examination is guaranteed to confirm and localise the abnormality. 

As understanding, technology and techniques have evolved so too have recommended imaging strategies. These will also depend on the local expertise. Generally, the approach should consist of:

1. confirming the presence of intracranial hypotension

2. confirming the presence of CSF leak

3. identifying the specific location and cause of CSF leak

Depending on the cause and location, these may be all achieved on the first study or require a number of different studies.

MRI of the brain with contrast

MRI of the brain is an essential first step, needed to confirm the diagnosis of intracranial hypotension and rule out other unexpected pathology.

Although intracranial hypotension is rarely caused by base of skull leaks, the setting of prior skull fracture or surgery, the addition of fat-saturated thin T2 weighted sequences are helpful in identifying an intracranial dural defect. This should also be added presumptively in patients who may have had undiagnosed pseudotumour cerebri (overweight young females) and targeted to the middle cranial fossa. 

MRI of the spine

Ideally this can be performed at the same time as the MRI of the brain but need not consist of a full mulitparameter study; heavily T2 weighted fat saturated sequences through the spinal canal and adjacement soft tissues suffice ²⁵. These can be performed as 3D sequences (ideally) or multiplanar 2D sequences.

In many instances this will not only confirm the presence of an epidural CSF collection, but also localise the likely site of leak (e.g. calcified thoracic disk).

Myelography

If further localisation of a leak is required then a variety of myelographic techniques are useful. Which is chosen depends what the initial imaging of the brain and spine have shown ²⁵ as well as on local preference, policies and available equipment and expertise.

There are five main options each with pros and cons:

1. dynamic CT myelography (prone or decubitus)

2. digital subtraction myelography

3. fluoroscopic myelography

4. MR myelography

5. nuclear medicine myelography

Dynamic CT myelography

Unlike traditional CT myelography where intrathecal contrast is introduced a significant time prior to the CT, often in the fluoroscopy room, allowing the contrast to mix evenly throughout the CSF, in dynamic CT myelography contrast is introduced with the patient already positioned in the CT scanner, either prone or decubitus depending on the likely cause of CSF leak and dense contrast visualised to identify the site of leakage ^24,25.

It should be noted that if the amount of leaked CSF is large, the distribution of fluid should not be interpreted as necessarily representing the site of leak ⁹. CSF in the epidural space can migrate over significant distances and pool depending on patient position and anatomy. Similarly, delayed myelography will show opacification of the entire epidural fluid collection and may misrepresent the site of leak.

A particular example of this is pooling of contrast/CSF at the C1/2 level posteriorly. This can be incorrectly attributed to a local leak, when in fact this is not the case. This is referred to as a false localising sign ^10-12. 

A recent study showed that renal excretion of contrast on CT myelogram is 100% specific for the presence of a CSF leak. Therefore, the identification of such finding should prompt a second look for a CSF leak ²².

Digital subtraction myelography

Digital subtraction myelography has the best temporal resolution, and with newer equipment allowing Dyna-CT, can also obtain cross-sectional images. This is particularly useful for CSF-venous fistulas.

MR myelography

MR myelography (with intrathecal gadolinium) is not approved by FDA and is associated with neurotoxicity, particularly if renal function or CSF hydrodynamics are compromised but it has been tried in some cases when other methods have failed to demonstrate the source of CSF leak ⁹. MR myelography with intrathecal gadolinium has been shown to be more sensitive than CT in that respect ⁶.

Nuclear medicine myelography

Nuclear medicine myelography can also be employed, using intrathecal ¹¹¹Indium-DTPA, with images obtained typically at 1, 2, 4, 24, and in some instances even 48 hours post-injection ⁹. Localisation can be seen as a focal accumulation of activity. In some cases, only indirect evidence of a leak being present somewhere is available, which is only really useful in instances where the diagnosis of CSF leak remains uncertain. Indirect evidence includes ⁹:

• early accumulation of activity within the urinary tract (kidneys/bladder) at 4 hours

• absent activity over the cerebral convexities at 24 hours

• rapid loss of activity from within the CSF space

Treatment and prognosis

A non-targeted epidural blood patch is often used in cases of spontaneous intracranial hypotension, on the assumption that the leak is from the spine, with variable success ⁹. When successful, headaches resolve within 72 hours of intervention ¹². Subdural effusions can resolve within a few days to weeks. Larger subdural collections often require far longer to resolve ¹². 

In cases where such speculative treatment fails, localisation of the CSF leak is required, allowing for targeted epidural blood patch or surgical intervention ⁹. 

Targeted epidural blood patch can either be performed using a translaminar approach, as for initial non-targeted injections or aimed at entering the ventral epidural space using a transforaminal approach at one or more levels and potentially from both sides ²⁰.