Timothy C. Hain, MD. Page last modified: July 20, 2014
Also see: nph and hydrocephalus
Cerebrospinal fluid depletion may be caused by a leak, a shunt, inadequate production or too rapid absorption. There are also some similar syndromes where the compliance of the intracranial compartment is too high, causing similar symptoms when the brain sags downward on standing, and floats back upward supine. It is estimated that CSF leaks have an incidence of about 5/100,000 per year.
Symptoms of CSF leak commonly include headaches, which are more severe in the upright position and are alleviated by supine or head-lowered below chest (Trendelenburg) positioning. Horizontal diplopia, change in hearing, tinnitus, blurring of vision, facial numbness, nausea, and upper limb radicular symptoms (tingling) may occur. These symptoms are nonspecific as they are commonly encountered in migraine and post-traumatic headache. Cognitive decline has also been reported (Hong et al, 2002; Pleasure et al, 1998).
The diagnostic criteria of the International Headache Society include:
Of these symptoms, neck pain or stiffness, nausea and vomiting are the most common symptoms. If we consider which symptoms are the most specific, this is obviously #3. The associated symptoms are common human complaints -- for example, severe tinnitus is endorsed by 6% of the population, and migraine headaches which commonly include photophobia and nausea affect roughly 15% of the entire population. Regarding #3, It has been our observation that brain MRI showing indirect signs of CSF pressure (i.e. dural enhancement) is rare.
Orthostatic HA without CSF Leak
Leep and Mokri (2008) reported that a small number of patients with typical orthostatic headaches lack radiological confirmation of CSF leak. They speculate that in these patients, there might be either an occult leak, or an abnormally distensible dura.
In the "trephine syndrome", similar symptoms are associated with a large skull defect (see image below), and are relieved by cranioplasty. (Stiver et al, 2008). One would think that there would be postural hearing fluctuations in the trephine syndrome, but to our knowledge, this has not been tested.
Postural headaches, generally on upright, may also occur in persons who are intermittently obstructing their CSF pathways such as in colloid cysts (see image below) or a cyst of the septum pellucidum.
Low CSF pressure without a leak being found, called "spontaneous intracranial hypotension", is rare, with a yearly incidence of about 5/100,000. These may be dectected from dural enhancement or lumbar puncture.
As this is an otoneurology site, we will go into the hearing related symptoms of CSF leaks in more detail. While CSF leak is generally accompanied by an orthostatic (upright only) headache, this association is not universal and in fact, hearing loss may be more common than headache (Oncel et al, 1992). Orthostatic tinnitus is also possible.(Arai, Takada et al. 2003). The hearing loss of CSF leak likely results from lowering of CSF pressure, which lowers perilymphatic (inner ear) pressure, and results in a picture similar to Meniere's disease. (Walsted et al., 1991).
|Shunt to drain ventricles. Shunts sometimes work too well and cause low CSF pressure.||MRI of patient with large craniotomy defect, potentially causing trephine syndrome (see above).||Colloid cyst of third ventricle -- these can intermittently obstruct, causing very severe orthostatic headaches.|
Acquired leaks can be caused by head or spine injury, surgery, infection or tumor. Leaks can occur in at dural root sleeves throughout the spine and may be a potential mechanism for orthostatic headache following motor vehicle accidents (Ishikawa et al, 2007).
Infections: Only 20 cases of leaks due to middle ear infection had been reported as of 2007 (Manjunath, 2007).
Congenital leaks are most often associated with the development of anomalous transcranial pathways.
Spontaneous leaks from the nose are uncommon (1/26 leaks in Mokri, 1997; 39/105 in Seth, 2010). According to Seth et al (2010), in 39 patients with spontaneous leaks, the most common sites were the cribriform plate (51%), the sphenous lateral pterygoid recess (31%), and ethmoid roof (8%). All of these locations are in the paranasal sinuses -- this is probably due to selection bias as this paper was a study done by nasal surgeons.
It would seem possible that CSF leaks might occur after whiplash injury, as frequently there are persistent similar symptoms without findings on other studies. Supporting this idea, CSF leaks have been reported due to cervical bone spurs (Miyazawa et al, 2003; Vishteh, Schievink et al. 1998). When we originally advanced this idea in 2002, almost nothing had been published regarding this possibility. Recently however, using radioisotope cisternography, Ishikawa et al, 2007 reported identification of CSF leaks primarily in the lumbar spine at the dural sleeves in 37 of 66 chronic whiplash patients with headache, memory loss, dizziness and neck pain.
Other things that can look like a leak
Other conditions to exclude when considering the diagnosis of CSF leak are orthostatic hypotension (which can cause dizziness on standing), positional vertigo due to inner ear disturbances such as BPPV, and orthostatic tremor. When considering leaks from the nose, of course other fluids than CSF can leak out of the nose. "Pseudo-CSF rhinorhea" can occur as a result of injury to the sphenopalatine ganglion (Hilinski et al, 2001).
CSF leaks can also result from high-pressure hydrocephalus. In this situation, leaks may recur until the cerebral ventricles are shunted (Tosun et al, 2003)
Before starting the discussion, lets first say that none of these techniques are very useful. The best, at the present time, involves using MRI to find side effects of low CSF pressure -- venous engorgement or downward displacement of the brain.
Head MRI findings include diffuse meningeal gadolinium enhancement due to engorgement of the cerebral venous system (Mokri et al, 1997, see page on dural enhancement), imaging evidence of sinking of the brain resembling the Chiari malformation (Paynor, 1994), subdural fluid collection, decrease in ventricular size and prominent dural sinuses.
Spine MRI may show extra-arachnoid fluid, meningeal diverticuli, meningeal enhancement, or engorgement of epidural venous plexi (Miyazawa et al, 2003; Medina et al, 2010; Starling et al, 2013; Bonetto et al, 2011).
The engorgement of the epidural venous plexus is analogous to the findings of meningeal enhancement on cerebral MRI. Engorgement may be missed if the MRI is read by a radiologist unfamiliar with this syndrome. Extradural fluid collections were reported in more than 85% of patients in several studies The collections were best visualized on axial T2, generally were located epidurally, and usually extended over 5 or more spinal segments. While this finding suggests that a CSF leak is possible, it does not identify the site of leak. It does not replace myelography.
Bonetto et al (2011) suggested that post-processing image analysis with subtraction of T1 from T2 weighted spinal MRI was highly successsful for identification of epidural leakage causing spontaneous intracranial hypotension. All of Bonetto's patients also had meningeal enhancement, and most had ventricular collapse. In other words, these were severe cases.
Response to abdominal binders is both used as a treatment as well as a diagnostic maneuver. (Schievink, 2008). It seems likely that compression garments, such as the "Zoot compression clothing", would work to even better effect.
|C1-C2 sign from J Neurol Neurosurg Psychiatry2003;74:821-822||Spinal hygroma found in patient with orthostatic headaches.|
The C1-C2 sign is a focal area of fluid between the spinous processes of C1 and C2 (image to left above). According to Medina et al, the C1-C2 level may be prone to fluid due to mobility, lack of epidural fat, and laxity of connective tissue at this level.
Spinal fluid hygromas (see image above to right), are similar fluid collections. When found in the setting of orthostatic headaches, they are a good reason to pursue the diagnosis of CSF leaks.Spontaneous leaks into the middle ear are usually diagnosed by high-resolution CT scans. This may reveal discrete tegmen defects, multiple pinhole fistulae, or a combination of these findings. About 6% of the population has some degree of bony defect. Most patients have an ipsilateral conductive or mixed hearing loss, the conductive component caused by CSF in the middle ear. These can be repaired via a middle fossa craniotomy (Leonetti et al, 2005).
It has been reported that doppler or MRI of the superior opthalmic vein may reveal abnormalities in persons with low CSF pressure (Chen et al. 1999; Chen et al., 2003). Doppler may show increased flow velocity. It may be difficult to find a sonographer with expertise in this method. We have not tried to use this method in Chicago -- and it also seems unlikely to work in any case.
MRI may show collapse of the superior opthalmic vein (Chen et al., 2003). Radiologists do not generally measure the diameter of the superior opthalmic vein, and if this technique is planned, it seems prudent to either seek out an experienced radiologist or develop the expertise through a series of MRI's done in normal persons. We have not had any success in this technique to date, but this may be simply because we have not seen an appropriate patient.
Leaks of spinal fluid from the nose or external ear can be detected by assaying the fluid with a new test called beta-trace protein assay (Bachman et al, 2002; Wernecke et al, 2004). It is too soon to say if this test will become widely available and useful. It is our thought that if there is so much fluid that it you can see it leaking in front of your eyes, you should use one of the spinal fluid tests instead.
Opening pressure on LP
In adults, CSF opening pressure is generally considered normal between 10 and 20 cm H20 (Wright et al, 2012). In normal children values may be even higher (28). A pressure less than 60 mm (6 cm) is suggestive of CSF leak.
Use of radioactive material into the spinal fluid is logical as it can be detected with extremely high sensitivity, and also there is no natural source for radioactive secretions. Radioactive label materials may include technetium or indium 111. Indium is an agent that attaches specifically to CSF proteins. A major disadvantage of the radioactive imaging is high cost and the possibility of false-positive results. This study requires injection of material into the spinal canal, a process which could introduce a CSF leak by itself. Radioisotope cisternography characteristically shows a decrease or absence of activity over the cerebral convexities and early accumulation of radioisotope in the bladder.
Radiologic studies are also useful --
CT contrast cisternography after metrizamide injection is considered to be the most useful during a leak. This may be impractical however if one does not know the level of the leak and can also be falsely localizing (Lue and Manolidis 2004). CT also requires radiation.
Gadolinium MRI documenting location of CSF leak (arrow). Image from Jinkins et al, 2002.
A new test, injection of a small amount of gadolinium contrast into the lumbar spinal fluid followed by MRI is very promising (Jinkins et al, 2002). Gadolinium is not as toxic as is CT contrast dye, and also while CT contrast could be confused with bony structures, gadolinium is not easily confused with other body parts. Of course, MRI can scan the entire neuroaxis if the site of leak is unclear. In our practice in Chicago, we obtain this test using a facility in Morton Grove Illinois (a suburb of Chicago). MRI is sometimes repeated at 1 and 2 days post injection, looking for intermittent leaks.
Although not recommended as a diagnostic test, on lumbar puncture, in approximately half of patients, the opening CSF pressure is 40 mm or less. However, if this is found, one still needs to locate the site of leak. The other half of patients may have normal CSF pressure so a lumbar puncture is not 100% reliable to diagnose low CSF pressure. Of course, there is some danger of causing a leak, per se, with a lumbar puncture, and the risks/benefits must be carefully considered. In a small minority of patients with CSF leak, CSF pressure may be normal although patients continue to have symptoms and abnormal MRI findings. Perhaps this indicates an intermittent situation.Spinal fluid testing may show a minor pleocytosis of 5 or more cells, and a modest and variable increase in protein (Mokri et al, 1997).
In the past it was thought that CSF could be distinguished from other fluids by it's glucose content. Testing of the fluid dripping from the nose for glucose is no longer thought to be useful. Testing for beta-transferrin may help determine if it is CSF or something else. We not difficult to implement, have not had much success with this method.
A surer method is to inject radioactive label or a fluorescent dye into the spinal fluid and test for the label or dye in the fluid. Nasal pledgets can be left in the nose for extended periods, enabling detection of intermittent rhinorhea. 0.5 ml of 5% fluorescein diluted in 9.5 cc of CSF is used (according to Hilinski et al, 2001). Smaller amounts are used in children. (Lue and Manolidis 2004). It is useful to use control pledgets under the upper lip for comparison. the test is analyzed under ultraviolet light. No complications were reported by Montgomery in more than 200 injections of fluorescein. Seth et al (2010) used this technique during surgery. However some authors have reported seizures from fluorscein can occur. For this reason, this method is not recommended.
|Mechanism through which CSF leaks cause hearing changes via endolymphatic hydrops(Michel and Brusis, 1992). This diagram shows the general idea but it is inaccurate as there are other pathways for CSF flow other than the cochlear aqueduct.|
Audiometry (hearing testing) is sometimes affected by CSF-leak. (Kilickan and Gurkan, 2003; Michel and Brusis 1992; Walsted, Salomon et al. 1991; Walsted, Salomon et al. 1991; Walsted, Salomon et al. 1993; Walsted, Salomon et al. 1993; Walsted, Nielsen et al. 1994; Walsted, Nilsson et al. 1996; Walsted, Salomon et al. 1996; Walsted 1998; Walsted 2000). The pattern of hearing loss may resemble that of Meniere's disease and exhibit a low-tone sensorineural pattern.
Although logically, hearing in persons with CSF leaks should improve in the supine position, as pressure goes up in the cranial compartment, this has been little studied. One would also think that tests that correlate with hearing, such as OAEs, could be postural too. Unfortunately, a confounding problem with both postural hearing and OAE testing, is that middle ear pressure may change with posture.
Treatment of CSF leak may include bed rest, hydration and steroids. Abdominal binders may be helpful. (Scheviak, 2008). Epidural blood patch as well as injection of fibrin glue is used in patients with spinal leaks who fail noninvasive measures. Blood patches are generally thought to be safe but occasional reports of increased CSF pressure and persistent epdurual fluid collections have been reported. Surgical repair is used in patients with leaks in the skull, and in the Trephine syndrome.
The overwhelming majority of patients have a spinal level leak, although they are generally higher than the lumbar level (Mokri, 1997). Surgical repair may be performed in patients that fail blood patch if the site of the leak has been identified.