Spontaneous cerebrospinal fluid leak
Encyclopedia
Spontaneous cerebrospinal fluid leak syndrome (SCSFLS) is a medical condition in which the cerebrospinal fluid
(CSF) held in and around a human brain and spinal cord leaks out of the surrounding protective sac, the dura
, for no apparent reason. The dura, a tough, inflexible tissue, is the outermost of the three layers of the meninges
, the system of meninges
surrounding the brain and spinal cord. (The other two meningeal layers are the pia mater
and the arachnoid mater
).
A spontaneous cerebrospinal fluid leak is one of several types of cerebrospinal fluid leak
s and occurs due to the presence of one or more holes in the dura. A spontaneous CSF leak, as opposed to traumatically caused CSF leaks, arises idiopathic
ally. A loss of CSF greater than its rate of production leads to a decreased volume inside the skull known as intracranial hypotension (ICH). A CSF leak is most often characterized by a severe and disabling headache and a spectrum of various symptoms which occur as a result of ICH. These symptoms can include: dizziness, nausea, fatigue, a metallic taste in the mouth (indicative of a cranial leak), myoclonus, tinnitus, tingling in the limbs, facial weakness
amongst others. A CT scan can identify the site of a cerebrospinal fluid leakage. Once identified, the leak can often be repaired by an epidural blood patch
, an injection of the patient's own blood at the site of the leak.
SCSFLS afflicts 5 out of every 100,000 people. On average, the condition is developed at the age of 42, and women are twice as likely as men to develop the condition. Some people with SCSFLS chronically leak cerebrospinal fluid despite repeated attempts at patching, leading to long-term disability due to pain and nerve damage. SCSFLS was first described by German neurologist Georg Schaltenbrand in 1938 and by American physician Henry Woltman of the Mayo Clinic in the 1950s.
. Cranial leaks occur in the head. In some cases, CSF can be seen dripping out of the nose, or ear. Spinal leaks occur when one or more holes form in the dura along the spinal cord. Both cranial and spinal spontaneous CSF leaks cause neurological symptoms as well as spontaneous intracranial hypotension, diminished volume and pressure of the cranium. While referred to as intracranial hypotension the intracranial pressure may be normal, but low-volume CSF is instead the underlying issue. For this reason SCSFLS is referred to as CSF hypovolemia as opposed to CSF hypotension.
Most people who develop SCSFLS feel a sudden onset of a severe and acute headache. It is an orthostatic headache
, in which the pain is worse when the patient is vertical and less severe when horizontal. Other symptoms include severe dizziness
and vertigo
, facial numbness or weakness, double vision
, fatigue, a metallic taste in the mouth, nausea
, and vomiting
. Leaking CSF can sometimes be observed as discharge through the nose or ear. Orthostatic headaches can be incapacitating; these symptoms can be sufficiently disabling to make those afflicted unable to work. Some patients with CSF leak will develop headaches that begin in the afternoon. This is known as second-half-of-the-day headache. This may be the initial presentation of CSF leak or appear after treatment and likely indicates a slow CSF leak.
Lack of CSF pressure and volume allows the brain to descend through the foramen magnum, or occipital bone, the large opening at the base of the skull. The lower portion of the brain is believed to stretch or impact one or more cranial nerve complexes, thereby causing a variety of sensory symptoms. Nerves that can be affected and their related symptoms are detailed in the table at right.
; it can arise spontaneously or from an unknown cause. Various scientists and physicians have suggested that this condition may be the result of an underlying connective tissue disorder affecting the spinal dura. It may also run in families and be associated with aortic aneurysms and joint hypermobility. Up to two thirds of those afflicted demonstrate some type of generalized connective tissue disorder. Marfan syndrome
, Ehlers-Danlos syndrome
and autosomal dominant polycystic kidney disease are the three most common connective tissue disorders associated with SCSFLS.
Roughly 20% of patients with SCSFLS exhibit features of Marfan syndrome, including tall stature, chest divot (pectus excavatum
), joint hypermobility
and arched palate. However these patients do not exhibit any other Marfan syndrome presentations.
vein.
Another view of the cause of orthostatic headaches proposes a malformed distribution of craniospinal elasticity as a result of the collapse of the lower spine's CSF space resulting in the collapse of the dura sac.
in the brain and contained by the dura and arachnoid layers of the meninges. The brain floats in CSF, which also transports nutrients to the brain and spinal cord. As holes form in the spinal dura mater, CSF leaks out into the surrounding space. The CSF is then absorbed into the spinal epidural venous plexus
or soft tissues around the spine. Due to the sterile conditions of the soft tissues around the spine there is no risk of meningitis.
s, meningitis
, and psychiatric disorders. The average time from onset of symptoms until definitive diagnosis is 13 months. A study found a 0% success rate for proper diagnosis in the emergency department.
Diagnosis of CSF leak can be done through various imaging techniques or chemical tests. The use of CT, MRI and assays are the most common types of CSF leak tests.
Diagnosis of a cerebrospinal fluid leak is performed through a combination of measurement of the CSF pressure and a computed tomography
myelogram (CTM) scan of the spinal column for fluid leaks. The opening fluid pressure in the spinal canal is obtained by performing a lumbar puncture
, also known as a spinal tap. Once the pressure is measured, radiopaque contrast
material is injected into the spinal fluid. The contrast then diffuses out through the dura sac before leaking through dural holes. This allows for a CTM with fluoroscopy
to locate and image any sites of dura rupture via contrast seen outside the dura sac in the imagery.
is historically less effective at directly imaging sites of CSF leak. MRI studies may show pachymeningeal enhancement (when the dura mater looks thick and inflamed) and an Arnold-Chiari malformation
many, but not all, cases. An Arnold-Chiari malformation occurs when the brain sags and has a downward displacement due to the decreased volume and buoyancy of cerebrospinal fluid in which the brain floats. MRIs can present as completely normal, however, and are not the study of choice. An alternate method of locating the site of a CSF leak is to use heavily T2-weighted MR myelography. This has been effective in identifying the sites of a CSF leak without the need for a CT scan, lumbar puncture, and contrast and at locating fluid collections such as CSF pooling. MRIs done on patients sitting upright demonstrated no difference in MRI results compared to those lying down. The use of intrathecal contrast and MR Meyrlography is also an alternative method of locating CSF leaks with a very high degree of success.
. This test can positively identify if the fluid is cerebrospinal fluid.
Patients with CSF leak have been noted to have very low or even negative opening pressures. However, patients with confirmed CSF leaks may also demonstrate completely normal opening pressures. In 18–46% of cases, the CSF pressure is measured within the normal range. Analysis of spinal fluid may demonstrate lymphocytic pleocytosis
and elevated protein content or xanthochromia. This is hypothesized to be due to increased permeability of dilated meningeal blood vessels and a decrease of CSF flow in the lumbar subarachnoid space.
es, which has a 90% success rate in treating dural holes; a rate higher than that of a conservative treatment of bed rest and hydration. Through the injection of a person's own blood into the area of the hole in the dura, an epidural blood patch uses blood's clotting factors to clot the sites of holes. The volume of autologous blood and number of patch attempts for patients is highly variable. One quarter to one third of SCSFLS patients do not have relief of symptoms from epidural blood patching.
can be used in place of blood patching, raising the effectiveness of forming a clot and arresting CSF leakage.
s.
People with cranial CSF leaks have a higher chance of developing meningitis than those with spinal CSF leaks. Additionally, if cranial leaks last more than seven days, the chances of developing meningitis are significantly higher. Spinal CSF leaks do not usually result in meningitis due to the mostly aseptic conditions of the spinal dura. When a CSF leak occurs at the temporal bone
surgery becomes necessary in order to prevent infection and repair the leak. Orthostatic hypotension
is another complication which occurs due to autonomic dysfunction when blood pressure drops significantly. The autonomic dysfunction is caused by compression of the brain stem
, which controls breathing and circulation.
An Arnold-Chiari malformation
is a downward displacement of lower parts of the brain through the skull opening that occurs due to a lack of CSF volume and pressure. A further, albeit rare, complication of CSF leak is transient quadriplegia
due to a sudden and significant loss of CSF. This loss results in hindbrain herniation
and causes major compression of the upper cervical spinal cord. The quadriplegia dissipates once the patient lays supine
. An extremely rare complication of SCSFLS is third nerve palsy
, where the ability to move one's eyes becomes difficult and interrupted due to compression of the third cranial nerve.
There are documented cases of reversible dementia
and coma
. Coma due to a CSF leak has been successfully treated by using blood patches and/or fibrin glue and placing the patient in the Trendelenburg position
. Empty sella syndrome
, a boney structure that surround the pituitary gland, occurs in CSF leak patients.
Studies have shown that SCSFLS runs in families and it is suspected that genetic similarity in families includes weakness in the dura mater, which leads to SCSFLS. Large scale population-based studies have not yet been conducted. While a majority of SCSFLS cases continue to be undiagnosed or misdiagnosed, an actual increase in occurrence is unlikely.
of the Mayo Clinic
wrote about "headaches associated with decreased intracranial pressure". The full clinical manifestations of intracranial hypotension and CSF leaks were described in several publications reported between the 1960s and early 1990s. Modern reports of spontaneous CSF leak have been reported to medical journals since the late 1980s.
Cosyntropin
, a corticosteroid that causes the brain to produce additional spinal fluid to replace the volume of the lost CSF and alleviate symptoms, has been used to treat CSF leaks.
In two small studies of two patients and another with one patient who suffered from recurrent CSF leaks where repeated blood patches failed to form clots and relieve symptoms, the patients received temporary but complete resolution of symptoms with an epidural saline infusion. The saline infusion temporarily restores the volume necessary for a patient to avoid SIH until the leak can be repaired properly. Intrathecal saline infusion is used in urgent cases such as intractable pain or decreased consciousness.
The gene TGFBR2 has been implicated in several connective tissue disorders including Marfan syndrome
, arterial tortuosity and thoracic aortic aneurysm
. A study of patients with SCSFLS demonstrated no mutations in this gene. Minor features of Marfan syndrome has been found in 20% of CSF leak patients. Abnormal findings of fibrillin-1 has been documented in these CSF leak patients but only one patient demonstrated a fibrillin-1 defect consistent with Marfan syndrome.
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
(CSF) held in and around a human brain and spinal cord leaks out of the surrounding protective sac, the dura
Dura mater
The dura mater , or dura, is the outermost of the three layers of the meninges surrounding the brain and spinal cord. It is derived from Mesoderm. The other two meningeal layers are the pia mater and the arachnoid mater. The dura surrounds the brain and the spinal cord and is responsible for...
, for no apparent reason. The dura, a tough, inflexible tissue, is the outermost of the three layers of the meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...
, the system of meninges
Meninges
The meninges is the system of membranes which envelopes the central nervous system. The meninges consist of three layers: the dura mater, the arachnoid mater, and the pia mater. The primary function of the meninges and of the cerebrospinal fluid is to protect the central nervous system.-Dura...
surrounding the brain and spinal cord. (The other two meningeal layers are the pia mater
Pia mater
Pia mater often referred to as simply the pia, is the delicate innermost layer of the meninges, the membranes surrounding the brain and spinal cord. The word finds its roots in Latin, meaning literally "tender mother." The other two meningeal membranes are the dura mater and the arachnoid mater....
and the arachnoid mater
Arachnoid mater
The arachnoid mater, literally from Latin "spider -like mother", is one of the three meninges, the membranes that cover the brain and spinal cord...
).
A spontaneous cerebrospinal fluid leak is one of several types of cerebrospinal fluid leak
Cerebrospinal fluid leak
A cerebrospinal fluid leak is a medical condition when the cerebrospinal fluid of a person leaks out of the dura mater. This can be caused by several reasons, including spontaneous cerebrospinal fluid leak, post-surgical lumbar puncture , physical trauma, etc...
s and occurs due to the presence of one or more holes in the dura. A spontaneous CSF leak, as opposed to traumatically caused CSF leaks, arises idiopathic
Idiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
ally. A loss of CSF greater than its rate of production leads to a decreased volume inside the skull known as intracranial hypotension (ICH). A CSF leak is most often characterized by a severe and disabling headache and a spectrum of various symptoms which occur as a result of ICH. These symptoms can include: dizziness, nausea, fatigue, a metallic taste in the mouth (indicative of a cranial leak), myoclonus, tinnitus, tingling in the limbs, facial weakness
Facial weakness
Facial weakness is a medical sign associated with a variety of medical conditions.Some specific conditions associated with facial weakness include:* stroke* neurofibromatosis* Bell's palsy* Ramsay Hunt syndrome* Spontaneous cerebrospinal fluid leak...
amongst others. A CT scan can identify the site of a cerebrospinal fluid leakage. Once identified, the leak can often be repaired by an epidural blood patch
Epidural blood patch
An epidural blood patch is a surgical procedure which uses autologous blood in order to close one or many holes in the dura mater of the spinal cord, usually as a result of a previous lumbar puncture. The procedure can be used to relieve post dural puncture headaches caused by lumbar puncture...
, an injection of the patient's own blood at the site of the leak.
SCSFLS afflicts 5 out of every 100,000 people. On average, the condition is developed at the age of 42, and women are twice as likely as men to develop the condition. Some people with SCSFLS chronically leak cerebrospinal fluid despite repeated attempts at patching, leading to long-term disability due to pain and nerve damage. SCSFLS was first described by German neurologist Georg Schaltenbrand in 1938 and by American physician Henry Woltman of the Mayo Clinic in the 1950s.
Classification
SCSFLS is classified into two main types, cranial leaks and spinal leaksSpinal canal
The spinal canal is the space in vertebrae through which the spinal cord passes. It is a process of the dorsal human body cavity. This canal is enclosed within the vertebral foramen of the vertebrae...
. Cranial leaks occur in the head. In some cases, CSF can be seen dripping out of the nose, or ear. Spinal leaks occur when one or more holes form in the dura along the spinal cord. Both cranial and spinal spontaneous CSF leaks cause neurological symptoms as well as spontaneous intracranial hypotension, diminished volume and pressure of the cranium. While referred to as intracranial hypotension the intracranial pressure may be normal, but low-volume CSF is instead the underlying issue. For this reason SCSFLS is referred to as CSF hypovolemia as opposed to CSF hypotension.
Signs and symptoms
| Nerve | Function | Symptoms | |
|---|---|---|---|
| optic Optic nerve The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of... (2) |
optic nerve crossing |
blurred vision | |
| chorda tympani Chorda tympani The chorda tympani is a nerve that branches from the facial nerve inside the facial canal, just before the facial nerve exits the skull via the Stylomastoid foramen... (Branch of 7) |
taste | taste distortion Dysgeusia Dysgeusia is the distortion of the sense of taste. Dysgeusia is also often associated with ageusia, which is the complete lack of taste, and hypogeusia, which is the decrease in taste sensitivity. An alteration in taste or smell may be a secondary process in various disease states, or it may be... |
|
| facial Facial nerve The facial nerve is the seventh of twelve paired cranial nerves. It emerges from the brainstem between the pons and the medulla, and controls the muscles of facial expression, and functions in the conveyance of taste sensations from the anterior two-thirds of the tongue and oral cavity... (7) |
facial nerve | facial weakness and numbness |
|
| vestibulocochlear Vestibulocochlear nerve The vestibulocochlear nerve is the eighth of twelve cranial nerves, and is responsible for transmitting sound and equilibrium information from the inner ear to the brain... (8) |
hearing, balance |
hearing and balance problems |
|
| glossopharyngeal Glossopharyngeal nerve The glossopharyngeal nerve is the ninth of twelve pairs of cranial nerves . It exits the brainstem out from the sides of the upper medulla, just rostral to the vagus nerve... (9) |
taste | taste distortion |
Most people who develop SCSFLS feel a sudden onset of a severe and acute headache. It is an orthostatic headache
Orthostatic headache
Orthostatic headache is a medical condition in which a person develops a severe headache while vertical and the headache is relieved when horizontal.-Causes:...
, in which the pain is worse when the patient is vertical and less severe when horizontal. Other symptoms include severe dizziness
Dizziness
Dizziness refers to an impairment in spatial perception and stability. The term is somewhat imprecise. It can be used to mean vertigo, presyncope, disequilibrium, or a non-specific feeling such as giddiness or foolishness....
and vertigo
Vertigo (medical)
Vertigo is a type of dizziness, where there is a feeling of motion when one is stationary. The symptoms are due to a dysfunction of the vestibular system in the inner ear...
, facial numbness or weakness, double vision
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
, fatigue, a metallic taste in the mouth, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
, and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
. Leaking CSF can sometimes be observed as discharge through the nose or ear. Orthostatic headaches can be incapacitating; these symptoms can be sufficiently disabling to make those afflicted unable to work. Some patients with CSF leak will develop headaches that begin in the afternoon. This is known as second-half-of-the-day headache. This may be the initial presentation of CSF leak or appear after treatment and likely indicates a slow CSF leak.
Lack of CSF pressure and volume allows the brain to descend through the foramen magnum, or occipital bone, the large opening at the base of the skull. The lower portion of the brain is believed to stretch or impact one or more cranial nerve complexes, thereby causing a variety of sensory symptoms. Nerves that can be affected and their related symptoms are detailed in the table at right.
Causes
The two main theories as to the underlying cause of SCSFLS are as a result of a connective tissue disorder or spinal drainage problems.Connective Tissue Theory
A spontaneous CSF leak is idiopathicIdiopathic
Idiopathic is an adjective used primarily in medicine meaning arising spontaneously or from an obscure or unknown cause. From Greek ἴδιος, idios + πάθος, pathos , it means approximately "a disease of its own kind". It is technically a term from nosology, the classification of disease...
; it can arise spontaneously or from an unknown cause. Various scientists and physicians have suggested that this condition may be the result of an underlying connective tissue disorder affecting the spinal dura. It may also run in families and be associated with aortic aneurysms and joint hypermobility. Up to two thirds of those afflicted demonstrate some type of generalized connective tissue disorder. Marfan syndrome
Marfan syndrome
Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....
, Ehlers-Danlos syndrome
Ehlers-Danlos syndrome
Ehlers–Danlos syndrome is a group of inherited connective tissue disorders, caused by a defect in the synthesis of collagen . The collagen in connective tissue helps tissues to resist deformation...
and autosomal dominant polycystic kidney disease are the three most common connective tissue disorders associated with SCSFLS.
Roughly 20% of patients with SCSFLS exhibit features of Marfan syndrome, including tall stature, chest divot (pectus excavatum
Pectus excavatum
Pectus excavatum is the most common congenital deformity of the anterior wall of the chest, in which several ribs and the sternum grow abnormally. This produces a caved-in or sunken appearance of the chest...
), joint hypermobility
Hypermobility
Hypermobility describes joints that stretch farther than is normal. For example, some hypermobile people can bend their thumbs backwards to their wrists, bend their knee joints backwards, put their leg behind the head or other contortionist performances...
and arched palate. However these patients do not exhibit any other Marfan syndrome presentations.
Spinal Drainage Theory
Some other studies have proposed that issues with the spinal venous drainage system may cause a CSF leak. According to this theory, dural holes and intracranial hypotension are symptoms caused by low pressure in the epidural space due to outflow to the heart through the inferior vena cavaInferior vena cava
The inferior vena cava , also known as the posterior vena cava, is the large vein that carries de-oxygenated blood from the lower half of the body into the right atrium of the heart....
vein.
Other causes
Patients with a nude (absent) nerve root are at increased risk for developing recurrent CSF leaks. Cranial CSF leaks are as a result of intracranial hypertension in a vast majority of cases. The increased pressure causes a rupture of the cranial dura mater, leading to CSF leak and intracranial hypotension. Lumbar disc herniation has been reported to cause CSF leak in at least one case. Degenerative spinal disc diseases cause a disc to pierce the dura mater, leading to a CSF leak.Another view of the cause of orthostatic headaches proposes a malformed distribution of craniospinal elasticity as a result of the collapse of the lower spine's CSF space resulting in the collapse of the dura sac.
Pathophysiology
Cerebrospinal fluid is produced by the choroid plexusChoroid plexus
The choroid plexus is a structure in the ventricles of the brain where cerebrospinal fluid is produced...
in the brain and contained by the dura and arachnoid layers of the meninges. The brain floats in CSF, which also transports nutrients to the brain and spinal cord. As holes form in the spinal dura mater, CSF leaks out into the surrounding space. The CSF is then absorbed into the spinal epidural venous plexus
Venous plexus
A venous plexus is a congregation of multiple veins.Examples of venous plexuses are:* Vesical venous plexus* Vaginal venous plexus* Uterine venous plexus*Pterygoid plexus...
or soft tissues around the spine. Due to the sterile conditions of the soft tissues around the spine there is no risk of meningitis.
Diagnosis
The primary place of first complaint to a physician is a hospital emergency room. Up to 94% of those suffering from SCSFLS are initially misdiagnosed. Incorrect diagnoses include migraineMigraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
s, meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
, and psychiatric disorders. The average time from onset of symptoms until definitive diagnosis is 13 months. A study found a 0% success rate for proper diagnosis in the emergency department.
Diagnosis of CSF leak can be done through various imaging techniques or chemical tests. The use of CT, MRI and assays are the most common types of CSF leak tests.
CT
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
myelogram (CTM) scan of the spinal column for fluid leaks. The opening fluid pressure in the spinal canal is obtained by performing a lumbar puncture
Lumbar puncture
A lumbar puncture is a diagnostic and at times therapeutic procedure that is performed in order to collect a sample of cerebrospinal fluid for biochemical, microbiological, and cytological analysis, or very rarely as a treatment to relieve increased intracranial pressure.-Indications:The...
, also known as a spinal tap. Once the pressure is measured, radiopaque contrast
Radiocontrast
Radiocontrast agents are a type of medical contrast medium used to improve the visibility of internal bodily structures in an X-ray based imaging techniques such as computed tomography or radiography...
material is injected into the spinal fluid. The contrast then diffuses out through the dura sac before leaking through dural holes. This allows for a CTM with fluoroscopy
Fluoroscopy
Fluoroscopy is an imaging technique commonly used by physicians to obtain real-time moving images of the internal structures of a patient through the use of a fluoroscope. In its simplest form, a fluoroscope consists of an X-ray source and fluorescent screen between which a patient is placed...
to locate and image any sites of dura rupture via contrast seen outside the dura sac in the imagery.
MRI
Magnetic resonance imagingMagnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
is historically less effective at directly imaging sites of CSF leak. MRI studies may show pachymeningeal enhancement (when the dura mater looks thick and inflamed) and an Arnold-Chiari malformation
Arnold-Chiari malformation
Arnold–Chiari malformation, or often simply Chiari malformation, is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils through the foramen magnum , sometimes causing non-communicating hydrocephalus as a result of obstruction of cerebrospinal fluid outflow...
many, but not all, cases. An Arnold-Chiari malformation occurs when the brain sags and has a downward displacement due to the decreased volume and buoyancy of cerebrospinal fluid in which the brain floats. MRIs can present as completely normal, however, and are not the study of choice. An alternate method of locating the site of a CSF leak is to use heavily T2-weighted MR myelography. This has been effective in identifying the sites of a CSF leak without the need for a CT scan, lumbar puncture, and contrast and at locating fluid collections such as CSF pooling. MRIs done on patients sitting upright demonstrated no difference in MRI results compared to those lying down. The use of intrathecal contrast and MR Meyrlography is also an alternative method of locating CSF leaks with a very high degree of success.
Assay
When cranial CSF leak is suspected because of discharge from the nose or ear that is potentially CSF, the fluid can be collected and tested with a beta-2 transferrin assayBeta-2 transferrin
Beta-2 transferrin is a carbohydrate-free isoform of transferrin, which is almost only found in the cerebrospinal fluid. It is not found in blood, mucus or tears, thus making it a specific marker of cerebrospinal fluid, applied as an assay in cases where cerebrospinal fluid leakage is...
. This test can positively identify if the fluid is cerebrospinal fluid.
CSF analysis
Lymphocytic pleocytosis
Lymphocytic pleocytosis is a neurological condition in which a patient has a migraine type headache and also has lymphocyte cells present in the spinal fluid. Many cases may be due to aseptic meningitis. LP causes transient neurological deficits, including sensory motor amnesia, aphasia and...
and elevated protein content or xanthochromia. This is hypothesized to be due to increased permeability of dilated meningeal blood vessels and a decrease of CSF flow in the lumbar subarachnoid space.
Clinical presentation
The diagnostic criteria for SCSFLS is based on the 2004 International Classification of Headache Disorders, 2nd edn (ICHD-II) (Table 1) (50) criteria. However, the presentation of patients with confirmed diagnosis may be very different from that of the clinical diagnostic criteria and cannot be considered authoritative.Epidural Blood Patch
The treatment of choice for this condition is the surgical application of epidural blood patchEpidural blood patch
An epidural blood patch is a surgical procedure which uses autologous blood in order to close one or many holes in the dura mater of the spinal cord, usually as a result of a previous lumbar puncture. The procedure can be used to relieve post dural puncture headaches caused by lumbar puncture...
es, which has a 90% success rate in treating dural holes; a rate higher than that of a conservative treatment of bed rest and hydration. Through the injection of a person's own blood into the area of the hole in the dura, an epidural blood patch uses blood's clotting factors to clot the sites of holes. The volume of autologous blood and number of patch attempts for patients is highly variable. One quarter to one third of SCSFLS patients do not have relief of symptoms from epidural blood patching.
Fibrin glue sealant
If blood patches alone do not succeed in closing the dural tears, placement of percutaneous fibrin glueFibrin glue
Fibrin glue is a formulation used to create a fibrin clot. It is made up of fibrinogen and thrombin that are injected through one head into the site of a fibrin tear. Thrombin is an enzyme and converts the fibrinogen into fibrin between 10 and 60 seconds and acts as a tissue adhesive. It may also...
can be used in place of blood patching, raising the effectiveness of forming a clot and arresting CSF leakage.
Surgical drain technique
In extreme cases of intractable CSF leak, a surgical lumbar drain has been used. This procedure is believed to decrease spinal CSF volume while increasing intracranial CSF pressure and volume. This procedure restores normal intracranial CSF volume and pressure while promoting the healing of dural tears by lowering the pressure and volume in the dura. This procedure has led to positive results leading to relief of symptoms for up to one year.Neurosurgical repair
For patients who do not respond to either epidural blood patching or fibrin glue, neurosurgery is available to directly repair leaking meningeal diverticula. The areas of dura leak can be tied together in a process called ligation and then a metal clip can be placed in order to hold the ligation closed. Alternatively, a small compress called a muscle pledget can be placed over the dura leak and then sealed with gel foam and fibrin glue. Primary suturing is rarely able to repair a CSF leak and in some patients exploration of the dura may be required to properly locate all sites of CSF leak.Prognosis
Final outcomes for people with SCSFLS remain poorly studied. Some of those afflicted continue to leak CSF from one or more sites and may suffer from unremitting symptoms for many years. People with chronic SCSFLS may be disabled and unable to work. Recurrent CSF leak at an alternate site after recent repair is common.Complications
Several complications can occur as a result of SCSFLS including decreased cranial pressure, brain herniation, infection, blood pressure problems, transient paralysis, and coma.The primary and most serious complication of SCSFLS is spontaneous intracranial hypotension, where pressure in the brain is severely decreased. This complication leads to the hallmark symptom of severe orthostatic headacheOrthostatic headache
Orthostatic headache is a medical condition in which a person develops a severe headache while vertical and the headache is relieved when horizontal.-Causes:...
s.
People with cranial CSF leaks have a higher chance of developing meningitis than those with spinal CSF leaks. Additionally, if cranial leaks last more than seven days, the chances of developing meningitis are significantly higher. Spinal CSF leaks do not usually result in meningitis due to the mostly aseptic conditions of the spinal dura. When a CSF leak occurs at the temporal bone
Temporal bone
The temporal bones are situated at the sides and base of the skull, and lateral to the temporal lobes of the cerebrum.The temporal bone supports that part of the face known as the temple.-Parts:The temporal bone consists of four parts:* Squama temporalis...
surgery becomes necessary in order to prevent infection and repair the leak. Orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
is another complication which occurs due to autonomic dysfunction when blood pressure drops significantly. The autonomic dysfunction is caused by compression of the brain stem
Brain stem
In vertebrate anatomy the brainstem is the posterior part of the brain, adjoining and structurally continuous with the spinal cord. The brain stem provides the main motor and sensory innervation to the face and neck via the cranial nerves...
, which controls breathing and circulation.
An Arnold-Chiari malformation
Arnold-Chiari malformation
Arnold–Chiari malformation, or often simply Chiari malformation, is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils through the foramen magnum , sometimes causing non-communicating hydrocephalus as a result of obstruction of cerebrospinal fluid outflow...
is a downward displacement of lower parts of the brain through the skull opening that occurs due to a lack of CSF volume and pressure. A further, albeit rare, complication of CSF leak is transient quadriplegia
Quadriplegia
Tetraplegia, also known as quadriplegia, is paralysis caused by illness or injury to a human that results in the partial or total loss of use of all their limbs and torso; paraplegia is similar but does not affect the arms...
due to a sudden and significant loss of CSF. This loss results in hindbrain herniation
Brain herniation
Brain herniation, also known as cistern obliteration, is a deadly side effect of very high intracranial pressure that occurs when the brain shifts across structures within the skull...
and causes major compression of the upper cervical spinal cord. The quadriplegia dissipates once the patient lays supine
Supine position
The supine position is a position of the body: lying down with the face up, as opposed to the prone position, which is face down, sometimes with the hands behind the head or neck. When used in surgical procedures, it allows access to the peritoneal, thoracic and pericardial regions; as well as the...
. An extremely rare complication of SCSFLS is third nerve palsy
Oculomotor nerve palsy
Oculomotor nerve palsy is an eye condition resulting from damage to the third cranial nerve or a branch thereof. As the name suggests, the oculomotor nerve supplies the majority of the muscles controlling eye movements. Thus, damage to this nerve will result in the affected individual being unable...
, where the ability to move one's eyes becomes difficult and interrupted due to compression of the third cranial nerve.
There are documented cases of reversible dementia
Frontotemporal dementia
Frontotemporal dementia is a clinical syndrome caused by degeneration of the frontal lobe of the brain and may extend back to the temporal lobe...
and coma
Coma
In medicine, a coma is a state of unconsciousness, lasting more than 6 hours in which a person cannot be awakened, fails to respond normally to painful stimuli, light or sound, lacks a normal sleep-wake cycle and does not initiate voluntary actions. A person in a state of coma is described as...
. Coma due to a CSF leak has been successfully treated by using blood patches and/or fibrin glue and placing the patient in the Trendelenburg position
Trendelenburg position
In the Trendelenburg position the body is laid flat on the back with the feet higher than the head by 15-30 degrees, in contrast to the reverse Trendelenburg position, where the body is tilted in the opposite direction. This is a standard position used in abdominal and gynecological surgery...
. Empty sella syndrome
Empty sella syndrome
Empty sella syndrome is a disorder that involves the sella turcica, a bony structure at the base of the brain that surrounds and protects the pituitary gland...
, a boney structure that surround the pituitary gland, occurs in CSF leak patients.
Epidemiology
A 1994 community-based study indicated that two out of every 100,000 people suffered from SCSFLS, while a 2004 emergency room-based study indicated five per 100,000. SCSFLS generally affects the young and middle aged; the average age for onset is 42.3 years, but onset can range from ages 22 to 61. In an 11-year study women were found to be twice as likely to be affected as men.Studies have shown that SCSFLS runs in families and it is suspected that genetic similarity in families includes weakness in the dura mater, which leads to SCSFLS. Large scale population-based studies have not yet been conducted. While a majority of SCSFLS cases continue to be undiagnosed or misdiagnosed, an actual increase in occurrence is unlikely.
History
Spontaneous CSF leaks have been described by notable physicians and reported in medical journals dating back to the early 1900s. German neurologist Georg Schaltenbrand reported in 1938 and 1953 what he termed "aliquorrhea", a condition marked by very low, unobtainable, or even negative CSF pressures. The symptoms included orthostatic headaches and other features that are now recognized as spontaneous intracranial hypotension. A few decades earlier, the same syndrome had been described in French literature as "hypotension of spinal fluid" and "ventricular collapse". In 1940, Henry WoltmanHenry Woltman
Henry Woltman was an American neurologist and the first neurologist at the Mayo Clinic in Rochester, MN. In his career as a research and clinical neurologist he discovered several new diseases, several of which still bear his name, including: Moersch-Woltman syndrome, the Woltman sign. Woltman...
of the Mayo Clinic
Mayo Clinic
Mayo Clinic is a not-for-profit medical practice and medical research group specializing in treating difficult patients . Patients are referred to Mayo Clinic from across the U.S. and the world, and it is known for innovative and effective treatments. Mayo Clinic is known for being at the top of...
wrote about "headaches associated with decreased intracranial pressure". The full clinical manifestations of intracranial hypotension and CSF leaks were described in several publications reported between the 1960s and early 1990s. Modern reports of spontaneous CSF leak have been reported to medical journals since the late 1980s.
Research and experimental treatments
IVIntravenous therapy
Intravenous therapy or IV therapy is the infusion of liquid substances directly into a vein. The word intravenous simply means "within a vein". Therapies administered intravenously are often called specialty pharmaceuticals...
Cosyntropin
Cosyntropin
Cosyntropin is a synthetic derivative of adrenocorticotropic hormone that is used in the ACTH stimulation test to evaluate and diagnose cortisol disorders...
, a corticosteroid that causes the brain to produce additional spinal fluid to replace the volume of the lost CSF and alleviate symptoms, has been used to treat CSF leaks.
In two small studies of two patients and another with one patient who suffered from recurrent CSF leaks where repeated blood patches failed to form clots and relieve symptoms, the patients received temporary but complete resolution of symptoms with an epidural saline infusion. The saline infusion temporarily restores the volume necessary for a patient to avoid SIH until the leak can be repaired properly. Intrathecal saline infusion is used in urgent cases such as intractable pain or decreased consciousness.
The gene TGFBR2 has been implicated in several connective tissue disorders including Marfan syndrome
Marfan syndrome
Marfan syndrome is a genetic disorder of the connective tissue. People with Marfan's tend to be unusually tall, with long limbs and long, thin fingers....
, arterial tortuosity and thoracic aortic aneurysm
Thoracic aortic aneurysm
A thoracic aortic aneurysm is an aortic aneurysm that presents primarily in the thorax.It is less common than an abdominal aortic aneurysm. However, a syphilitic aneurysm is more likely to be a thoracic aortic aneurysm than an abdominal aortic aneurysm....
. A study of patients with SCSFLS demonstrated no mutations in this gene. Minor features of Marfan syndrome has been found in 20% of CSF leak patients. Abnormal findings of fibrillin-1 has been documented in these CSF leak patients but only one patient demonstrated a fibrillin-1 defect consistent with Marfan syndrome.