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Last updated:
September 01, 2020
Years published: 2017, 2020
NORD gratefully acknowledges Connie Deline, MD, Spinal CSF Leak Foundation, and Wouter I. Schievink, MD, Professor of Neurosurgery, Department of Neurosurgery, Cedars-Sinai, for the preparation of this report.
Summary
Spontaneous intracranial hypotension is secondary to a cerebrospinal fluid (CSF) leak at the level of the spine and the resulting loss of CSF volume that bathes the brain and spinal cord. Males and females of all ages are affected, but the diagnosis is more common in females. Annual incidence of 5 per 100,000 is likely an underestimate, and the overall prevalence is unknown. It most often results in a new-onset headache that is worse with upright posture, along with other neurologic signs and symptoms. Variability in presenting signs and symptoms, along with low awareness of the disorder, contribute to delayed diagnosis, although this is improving with a growing volume of publications. Diagnostic imaging is quite specialized, both in techniques and in interpretation. Because there is a structural cause, a hole or defect in the spinal dura (a tough layer of connective tissue) that normally holds cerebrospinal fluid in, it is both treatable and curable. The most common treatment is epidural patching with blood or fibrin sealant, though surgery is sometimes needed. Outcomes are good for most patients.
Onset of symptoms and signs may be relatively abrupt or more gradual. Patients may be minimally affected or profoundly disabled with limited ability to function while upright.
The hallmark of intracranial hypotension is a positional headache. This headache is worse when upright and improves when lying down. It usually occurs within 15 minutes of assuming the upright position and is relieved after lying down within 15-30 minutes, however it may take hours to worsen or improve with change of position. Over time, the positional aspect of the headache tends to lessen and may even disappear. The location of the headache is most often in the back of the head or base of the skull, but can also occur in the front, sides or all over the head. The headache is rarely on just one side of the head. The quality of the headache is often described as a “pulling sensation” from the back of the head to the neck. The severity of the headache can range from mild to very severe and disabling.
Other characteristic symptoms include neck pain, neck stiffness, nausea, vomiting, sensitivity to light and/or sound, sense of imbalance, ringing in the ears, changes in hearing, and profound fatigue. Pain between the shoulder blades and into the upper arms is commonly reported. Patients may also experience visual changes, dizziness or vertigo, facial numbness or pain, or changes in taste.
Specific signs are often seen on brain MRI and are described below under the diagnosis section.
Atypical and serious neurologic complications do occur, so prompt recognition and treatment in such cases is important. Rarely, patients can present with signs and symptoms typical of behavioral variant frontotemporal dementia, Parkinsonism, superficial siderosis, ataxia (very unsteady gait) or quadriplegia. Cerebral venous thrombosis, stupor or coma, seizures, stroke and death have also been reported.
The underlying cause of spontaneous intracranial hypotension is a loss of cerebrospinal fluid (CSF) volume through a hole or tear in the spinal dura. The dura is the tough outermost layer of the meninges (connective tissues that surround the brain and spinal cord) that holds in the CSF. When this fluid volume is reduced, there is less fluid available to cushion the brain inside the skull. This loss of CSF causes headache and other neurological signs and symptoms and may result in a range of complications. With upright posture, the loss of CSF volume has a greater effect on the brain.
There is evidence that an underlying weakness of the spinal dura is present in a subset of cases. Several heritable (genetic) disorders of connective tissue (HDCT) have been associated with spontaneous intracranial hypotension. See related disorders below.
Also, many cases are associated with calcified discs and bone spurs of the spine that can tear the dura on the front side of the spinal cord.
The etiology of the CSF-venous fistula type of leak, first recognized in 2014, is not yet understood.
CSF leaks that occur spontaneously in the head (base of the skull) are not causally associated with intracranial hypotension.
Males and females of any age may develop spontaneous intracranial hypotension, although this is diagnosed more often in females. The peak age of diagnosis is age 40.
The prevalence of spontaneous intracranial hypotension is unknown. It is suspected that many cases never present for medical care, or resolve without treatment. The best estimate that we have of annual incidence is from an emergency department study done in Los Angeles, California. In this retrospective study, spontaneous intracranial hypotension was diagnosed half as frequently as subarachnoid hemorrhage (brain bleeding from an aneurysm), with an estimated incidence of about 5 cases per 100,000 per year. This is almost certainly an underestimate because the study was single-center and retrospective, and many patients likely remained undiagnosed.
The diagnosis of spontaneous intracranial hypotension is initially suspected based on presenting signs and symptoms. Many physician specialties may be involved in the care of patients, including primary care physicians, emergency medicine physicians, neurologists, neuroradiologists, pain management physicians, anesthesiologists, neurosurgeons, and geneticists.
Effective October 1, 2020, the specific diagnostic code for spontaneous intracranial hypotension is G96.811, and the specific code for spontaneous spinal CSF leak is G96.02.
When this diagnosis is suspected, magnetic resonance imaging (MRI) study of the brain with contrast should be done to look for several specific findings. These findings may be absent in up to 20% of cases, more often when this imaging is done weeks or months after onset. The mnemonic SEEPS is used by physicians to recall the findings:
S – subdural fluid collections
E – enhancement of the meninges (layers around the brain)
E – engorgement of venous structures
P – pituitary hyperemia (swelling)
S – sagging of the brain
A lumbar puncture may be done to measure the CSF opening pressure, but because this often falls in the normal range, it has limited value.
For many patients, spinal imaging to localize their spinal CSF leak may not be necessary, because one or more epidural blood patch procedures will be curative. See the treatment section below.
Different types of spinal CSF leaks have been observed based on findings of spinal imaging and at surgery. Treatment approaches are then tailored to the type and location of the leak. Type 1 CSF leaks are caused by a dural tear located ventral to (in front of) the spinal cord (type 1a) or posterolateral to (behind and to the side of) the spinal cord (type 1b). Type 2 CSF leaks are associated with simple (type 2a) or complex (type 2b [dural ectasia]) meningeal diverticula. Type 3 CSF leaks are CSF-venous fistulas. Type 4 CSF leaks are of indeterminate origin.
Noninvasive imaging in the form of a full spine MRI is preferred as the initial spinal imaging. The findings on spinal MRI guide the need for additional specialized spinal imaging techniques, including standard or dynamic computed tomography (CT), digital subtraction, and intrathecal gadolinium-enhanced MR myelography. The yield of imaging can be impacted by patient positioning and respiratory phase. The identification of the type and location of the spinal CSF leak is needed for further treatment planning. Current imaging techniques are not sensitive enough to identify a spinal CSF leak in all cases, thus negative imaging does not rule out the disorder. This limited sensitivity also impacts treatment options.
When there are findings on history, clinical exam, or imaging that suggest the presence of a heritable disorder of connective tissue, referral to a physician with expertise in these disorders may be of value. These patients may be at higher risk of cardiovascular abnormalities noted above under “related disorders”. Screening with echocardiography and/or other tests may be considered on a case by case basis.
Treatment
An uncertain percentage of patients with spontaneous intracranial hypotension have milder symptoms and/or symptoms that may resolve without any treatment. Simple measures including bed rest, fluids for hydration and caffeine intake may help to reduce the severity of symptoms.
In the setting of serious complications, such as coma or large subdural hematomas, urgent treatment will be needed.
For less emergent cases, when symptoms are significant or persistent, the most common initial treatment is a non-targeted epidural blood patch. In this procedure, some blood is taken from the patient’s arm vein and is injected into the spinal canal in the space outside the dura. Epidural patching procedures may also include the use of fibrin sealant and may be targeted to specific spinal levels. Neuroradiologists and anesthesiologists are physician subspecialties that perform these procedures most often. These procedures may be repeated several times if the improvement is incomplete or does not last.
When non-surgical procedures are ineffective or symptoms relapse, a neurosurgical repair may be necessary but relies upon imaging localization of the spinal CSF leak.
Following treatment, it is not uncommon for patients to develop rebound intracranial hypertension (elevated CSF pressure), which may persist for a variable length of time. The natural history and optimal treatment for this complication have not yet been well studied. Currently, acetazolamide is the most commonly used medication.
Most patients do very well, although some patients do have relapsing or persistent symptoms and disability.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
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