Timothy C. Hain, MD. Page last modified: April 20, 2011

Cerebrospinal fluid depletion may be caused by a leak, a shunt, inadequate production or too rapid absorption.

Symptoms 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).

Orthostatic headaches without CSF leak are rare. 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. Postural headaches, generally on upright, may also occur in persons who are intermittently obstructing their CSF pathways such as in colloid cysts or a cyst of the septum pellucidum.

As this is an otoneurology site, we will go into the hearing related symptoms in a bit 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.

Locations of CSF leaks

• CSF leaks are typically at the level of the spine, particularly the thoracic spine and cervicothoracic junction.
• Sometimes they are unintentional consequences of an overdraining CSF shunt (e.g. VP shunt), placed for CSF hypertension (hydrocephalus) -- see image above. (Pudenz and Folz, 1991)
• They can follow spinal surgery (Sin, 2006), where there may be a tear in the dura that surrounds the spinal cord.
• CSF leaks can also occur in the ear through weaknesses in the roof of the middle ear (see movie below).
  • Movie of CSF pulsations in ear tube(1,5 meg) (From Richard Wiet, M.D.)
  • CSF leaks into the middle ear are probably rare, although large numbers have been reported (Leonetti et al, 2005). CSF leaks into the middle ear are accompanied by serous otitis. The leaks can be acquired, congenital or spontaneous. Potential sites of CSF leak include the oval and round windows, the stapes footplate and the promentory.
  • In theory, a ventilation tube should not be put into an ear with a CSF leak, as this might provide a route for infection to enter the brain. Practically however, the middle ear is not sterile --and it communicates with the nose through the eustachian tube. We also do not know of any study in which infection rates with and without tube were compared -- thus it seems to us that this idea is not only purely theoretical, somewhat illogical, and also unverifiable.
  • To be sure that there is no CSF leak, one would need to do a high-resolution temporal bone CT scan in every person with otitis media with effusion. At this writing, perhaps because of the rarity of CSF leaks, this is not generally done. Instead, if continuous drainage of clear fluid is noted through the ventilation tube (as shown above), this observation leads to the diagnosis of a CSF leak from the ear. The video above (courtesy of Dr. R. Wiet, who was referred this patient with the tube in place), shows CSF pulsating in a ventilation tube.
• Sinus surgery and pituitary surgery are the main sources of leaks through the nose. The "Dandy maneuver" -- bending forward, and straining to see if this produces clear nasal discharge, can be used to diagnose these types of leaks if they are large ones.
• CSF leaks may follow diagnostic or therapeutic lumbar puncture as well as spinal anesthesia and after an inadvertant puncture of the dura following epidural anesthesia or epidural steroid injections (Johkura et al. 2000). In this case, the leak is at the site of the puncture. Symptoms from this kind of leak can be delayed for as long as a month (Lybecker and Anderson, 1995). It seems likely that these cases are often missed.

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

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)

Diagnostic testing

Tests not requiring lumbar puncture:

• MRI of head (engorgement, Chiari, subdural)
• Spine MRI
• High-resolution CT scan of temporal bone (if there are ear symptoms).

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). The engorgement of the epidural venous plexus is analogous to the findings on cerebral MRI. This finding may be missed if the MRI is read by a radiologist unfamiliar with this syndrome.   Extradural fluid collections were reported in 85% of patients studied by Medina et al.  The collections were best visualized on axial T2, generally were located epidurally, and usually extended over 5 or more spinal segments.

C1-C2 sign from J Neurol Neurosurg Psychiatry2003;74:821-822

The C1-C2 sign is a focal area of fluid between the spinous processes of C1 and C2.  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.

Other tests that have not been generally adopted

Recently 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.

Tests requiring lumbar puncture:

• Radioisotope cisternography (early appearance of tracer in kidneys or urinary bladder, parathecal activity, slow tracer ascent, paucity of activity over hemispheres at 24 hours)
• CT or MR myelography (extra-CSF dye)
• Fluorescein injection into spinal fluid.

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.

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).

Radioisotope cisternography characteristically shows a decrease or absence of activity over the cerebral convexities and early accumulation of radioisotope in the bladder. This study is somewhat invasive, requiring injection of material into the spinal canal.

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 non-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.

Older methods, not recommended at this date

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 should improve in the supine position, this has been little studied.

Treatment

Treatment may include bed rest, hydration and steroids. Epidural blood patch 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.

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.

REFERENCES:

• Bachman and others. Incidence of occult cerebrospinal fluid fistula during perinasal sinus surgery. Arch Otol HNS, 2002, 128, 1299-302
• Chen CC, Luo CL, Wang SJ, Chern CM, Fuh JL, Lin SH and Hu HH (1999). "Colour doppler imaging for diagnosis of intracranial hypotension." Lancet 354(9181): 826-9.
• Chen WT, Fuh JL, Lirng JF, Lu SR, Wu ZA and Wang SJ (2003). "Collapsed superior ophthalmic veins in patients with spontaneous intracranial hypotension." Neurology 61(9): 1265-7.
• Hilinski JM, Kim T, Harris JP. Posttraumatic pseudo-cerebrospinal fluid rhinorhea. Otol Neurotol 22:701-05, 2001
• Hong M, Shah GV, Adams KM et al. spontaneous intracranial hypotension causing reversible frontotemporal dementia. Neurology 2002:58:1285-87
• Ishikawa S, Yokoyama M, Mizobuchi S, Hashimoto H, Moriyama E, Morita K. Epidural blood patch therapy for chronic whiplash-associated disorder. Anesthesia and Analgesia 2007;105:809–814.
• Jinkins JR, M Rudwan, MD, G Krumina, and E. Tali. Intrathecal Gadolinium-enhanced MR Cisternography in the Evaluation of Clinically Suspected Cerebrospinal Fluid Rhinorrhea in Humans: Early Experience. Radiology 2002;222:555-559.
• Johkura, K., Y. Matsushita, et al. (2000). "Transient hearing loss after accidental dural puncture in epidural block." Eur J Neurol 7(1): 125-6.
• Kilickan, L., Y. Gurkan, et al. (2003). "The effect of combined spinal-epidural (CSE) anaesthesia and size of spinal needle on postoperative hearing loss after elective caesarean section." Clin Otolaryngol 28(3): 267-72.
• Leonetti JP and others. Spontaneous transtemporal CSF leakage: A study of 51 cases. ENT J. 84:11, 700-706, 2005,
• Leep Hunderfund, A. N. and B. Mokri (2008). "Orthostatic headache without CSF leak." Neurology 71(23): 1902-6.
• Lue, A. J. and S. Manolidis (2004). "Intrathecal fluorescein to localize cerebrospinal fluid leakage in bilateral Mondini dysplasia." Otol Neurotol25(1): 50-2.
• Lybecker, H. and T. Andersen (1995). "Repetitive hearing loss following dural puncture treated with autologous epidural blood patch." Acta Anaesthesiol Scand 39(7): 987-9.
• Manjunath B. CSF otorrhea presenting in complicated suppurative otitis media. ENT Jnl. 86:4, 223-225, 2007
• Medina JH, Abrams K, Falcone S, Bhatia RG. Spinal image findings in spontaneous intracranial hypotension. AJR:195,2010, 459-464
• Miyazawa K and others. CSF hypovolemia vs intracranial hypotension in "spontaneous intracranial hypotension syndrome". Neurology 2003:60:941-947
• Michel, O. and T. Brusis (1992). "Hearing loss as a sequel of lumbar puncture." Ann Otol Rhinol Laryngol 101(5): 390-4.
• Mokri B, Piepgras DG, Miller GM. Syndrome of orthostatic headaches and diffuse pachymeningeal gadolinium enhancement. Mayo Clin Proc 1997:72:400-413
• Mokri B, Atkinson JLD. False pituitary tumor in CSF leaks. Neurology 2000:66:573-575
• Mokri B, Posner JB. Spontaneous intracranial hypotension. The broadening clinical and imaging spectrum of CSF leaks. Neurology 2000:55:1771-1772
• Montcomery WW. repair of dural defects. In Surgery of the upper respiratory system, 2nd ed, Vol 1, Philadelphia: Lea and Febiger, 1979
• Oncel, S., L. Hasegeli, et al. (1992). "The effect of epidural anaesthesia and size of spinal needle on post-operative hearing loss." J Laryngol Otol 106(9): 783-7.
• Payner TD, Prenger E, Berger TS, Crone KR. Acquired Chiari malformations: incidence, diagnosis, and management. Neurosurgery 1994;34:429-434; discussion 434.
• Pleasure Sj and others. Spontaneous intracranial hypotension resulting in stupor caused by diencephalic compression. Neurology 1998:50:1854-57
• Pudenz, R. H. and E. L. Foltz (1991). "Hydrocephalus: overdrainage by ventricular shunts. A review and recommendations." Surg Neurol 35(3): 200-212.
• Seth R, Rajasekaran K, Luong A, Benninger MS, Batra PS. Spontaneous CSF Leaks: Factors predictive of additional interventions. Laryngoscope 120:2141–2146,2010
• Sin AH, Caldito G, Smith D, Rashidi M, Willis B, Nanda A. Predictive factors for dural tear and cerebrospinal fluid leakage in patients undergoing lumbar surgery. J Neurosurg Spine 2006;5:224-227.
• Tosun F, Carrau RL, Snyderman CH, Kassam A, Celin S, Schaitkin B. Endonasal endoscopic repair of cerebrospinal fluid leaks of the sphenoid sinus. Arch Otolaryngol Head Neck Surg 2003 May;129(5):576-80
• Vishteh AG, Schievink WI, Baskin JJ and Sonntag VK (1998). "Cervical bone spur presenting with spontaneous intracranial hypotension. Case report." J Neurosurg 89(3): 483-4.
• Walsted, A. (1998). "Effects of cerebrospinal fluid loss on the auditory system. Clinical and experimental investigations." Dan Med Bull 45(3): 268-81.
• Walsted, A. (2000). "Effects of cerebrospinal fluid loss on hearing." Acta Otolaryngol Suppl 543: 95-8.
• Walsted, A., O. A. Nielsen, et al. (1994). "Hearing loss after neurosurgery. The influence of low cerebrospinal fluid pressure." J Laryngol Otol 108(8): 637-41.
• Walsted, A., P. Nilsson, et al. (1996). "Cerebrospinal fluid loss and threshold changes. 2. Electrocochleographic changes of the compound action potential after CSF aspiration: an experimental study." Audiol Neurootol 1(5): 256-64.
• Walsted, A., G. Salomon, et al. (1991). "Low-frequency hearing loss after spinal anesthesia. Perilymphatic hypotonia?" Scand Audiol 20(4): 211-5.
• Walsted, A., G. Salomon, et al. (1993). "[Hearing loss after spinal anesthesia. An audiological controlled trial]." Ugeskr Laeger 155(38): 3009-11.
• Walsted, A., G. Salomon, et al. (1991). "Hearing decrease after loss of cerebrospinal fluid. A new hydrops model?" Acta Otolaryngol 111(3): 468-76.
• Walsted, A., G. Salomon, et al. (1996). "Cerebrospinal fluid loss and threshold changes. 1. Hearing loss in the contralateral ear after operation for acoustic neuroma: an analysis of the incidence, time course, frequency range, size and pathophysiological considerations." Audiol Neurootol 1(5): 247-55.
• Walsted, A., G. Salomon, et al. (1993). "[Reversible hearing loss in the contralateral ear after surgery of acoustic neurinoma]." Ugeskr Laeger 155(38): 3012-5.
• Warnecke A and others. Diagnostic relevance of beta-2 transferrin for detection of cerebrospinal fluid fistulas. Arch Otolaryngol Head Neck Surg; 130:1178-1184