The intracranial cavity consists of three components: cerebrospinal fluid (CSF), blood, and brain tissue. CSF is contained within the subarachnoid space between the arachnoid and pia layers of the meninges. CSF is produced by a specialized vascular structure called choroid plexus within each ventricle of the brain. A blood-CSF barrier is formed by ependymal cells that line the ventricles and choroid epithelial cells that line the surrounding capillaries within the choroid plexus.
The ventricular system includes two lateral ventricles, a third ventricle, and the fourth ventricle, which is encompassed by the brainstem and cerebellum. The interventricular foramen of Monro connects the third and lateral ventricles while the third and fourth ventricles communicate via the cerebral aqueduct, also known as the Aqueduct of Sylvius. CSF enters the subarachnoid space surrounding the brain and spinal cord via the foramina of Luschka and Magendie. It then travels within and around the brain and spinal cord until it is eventually reabsorbed by the arachnoid granules to finally make its way into the dural venous sinuses, back into the bloodstream.
Normal CSF pressure falls approximately within 65 to 195 mm of water or CSF within the subarachnoid space. Intracranial hypotension (ICH) is defined as CSF pressure less than 60 mm H2O. It is hypothesized that low CSF volume, as opposed to low CSF pressure, is the primary cause of symptoms of ICH.
Historically, Heinrich Irenaeus Quincke was credited with performing the first lumbar puncture (LP) in 1891. In 1898 it was August Bier, also known as the father of spinal anesthesia, who reported his observations on post-dural puncture headaches and proposed the hypothesis that ongoing leak of CSF from the dural puncture site was the inciting factor of such symptoms. His studies led to the proposition that the CSF leak exceeded the rate of CSF production. George Schaltenbrand, a German Neurologist, studied the pressure system of CSF within the cranial system. He proposed three mechanisms in which spontaneous ICH, which he termed "aliquorrhea," induce a clinical presentation identical to that of a post-LP headache. These mechanisms are a decrease in CSF production, an increase in CSF absorption, and loss of CSF volume via a leak.
The etiology of intracranial hypotension can be separated into two categories: spontaneous and iatrogenic. Iatrogenic ICH typically relates to continuous CSF leak into the epidural space following dural disruption secondary to LP. It has been observed that the removal of around 10% of CSF via LP induces orthostatic or postural headache in the average adult. This is clinically referred to as Lumbar Puncture Headache. Physicians theorize that a decrease in spinal CSF induces an increase in caudal CSF space compliance, which in turn leads to an abnormal distribution of craniospatial elasticity. This, in turn, causes further ICH and venous dilation in the upright position.
Several causes of spontaneous ICH have been hypothesized. The most widely accepted idea amongst the scientific community is the mechanism of a CSF leak. This primary theory describes CSF leak by disruption of the meninges in the spine. Minor trauma, such as twist or stretch of the meninges, has been found in many cases to cause rupture of underlying spinal epidural cysts or tear in the dural nerve sheath. Dural tear has been identified as the second most common cause of CSF leak, while leaks from meningeal diverticula represent the leading cause. Notably, several studies have found the latter to be the case in patients with underlying connective tissue disorders, such as Marfan's syndrome, due to predisposition for dural diverticula.
Spinal CSF-venous fistulas have been found to induce CSF hypovolemia by a mechanism of CSF leaking from the subarachnoid space into the venous system. CSF-venous fistulas are the third leading cause of CSF leak, although only making up about 2.5% of cases.
The majority of CSF leaks occur within the spine, specifically the thoracic or cervicothoracic junction. Rarely, CSF leaks can occur at the skull base, although it is controversial whether this anatomical region of CSF leak relates to cases of spontaneous ICH and orthostatic headache. One study suggested that patients presenting with an orthostatic headache should be presumed to have a spinal source for CSF leak even if there is already evidence of skull base CSF leak.
Although controversial, it is thought that low venous pressure could induce spontaneous ICH via low venous pressure within the inferior venous cava system, typically when blood is displaced to the lower extremities during activity. This induces venous hypotension within the epidural venous system, which in turn causes a decrease in the outflow of CSF along the spinal cavity. In this scenario, CSF leaks are precipitated from existing dural diverticula or cysts and thought to be a resulting factor of low epidural venous pressure.
Based on a systematic review of ICH literature, the annual incidence to be approximately 5 in 100,000. The peak age of this condition is around 40 years old, with a female to male ratio of 2 to 1. Thus, ICH should be considered in cases of postural headache in young or middle-aged adult patients.
It is theorized that headache in the setting of ICH occurs secondary to the traction of sensory innervated meningeal and intracranial structures. Also, the vasodilatory response of cerebral blood vessels to compensate for the decrease in CSF volume is believed to be a factor as well. There is evidence to support the fact that venous sinus distension induces pain and is a likely cause of headache in ICH cases.
Studies have shown that biopsies of meninges typically appear normal in patients with ICH. In acute cases, abnormal histopathological findings suggest meningeal reaction and hyperplasia of arachnoid cells. This reaction becomes more pronounced in patients with persistent symptoms. It is believed that the proliferation of the arachnoid cells occurs secondary to chronic venous hypervolemia and changes within layers of the deep dura during ICH. In one report, seven patients with spontaneous ICH underwent meningeal biopsy, one revealed: "non-specific inflammation." Another study found a single meningeal biopsy with "fibrocollagenous proliferation in the leptomeninges without evidence of inflammation." (Level 5). Several cases have identified meningeal fibrosis in some patients with prolonged ICH, with a disease course up to 6 weeks.
The primary symptomatic complaint of patients diagnosed with either spontaneous or iatrogenic ICH is a headache. Specifically, orthostatic (or postural) headache is reported, which was defined as headache induced with the free drainage of approximately 10% of total CSF volume. A postural headache occurs or worsens with upright positioning and typically improves once the patient lies in a recumbent position. Occasionally patients will report associated nausea, vomiting, and neck pain or stiffness. The onset typically occurs within 2 hours, most within 15 minutes. There have been a wide variety of associated symptoms reported, such as changes in hearing, anorexia, vertigo, dizziness, blurry vision, diplopia, photophobia, hiccups, unsteady gait.
Lumbar puncture was the first diagnostic tool that recognized changes in CSF pressure indicative of benign ICH. As previously mentioned, an opening pressure of 0 to 70 mmH2O was required to make this diagnosis. Lumbar puncture is no longer utilized as a first-line diagnostic procedure to diagnose ICH. Also, many patients with this syndrome are found to have normal CSF opening pressure on LP. The MRI brain has superseded LP in the diagnostic evaluation of suspected ICH.
Radiographic findings in cases of benign ICH most often present on MRI as Subdural fluid collections, enhancement of the pachymeninges, Engorgement of the venous structures, Pituitary enlargement, and Sagging of the brain, which can be referred to by the acronym SEEPS. The most common of these findings is pachymeningeal enhancement, which is thought to represent venous or craniospinal hypervolemia. However, this finding is nonspecific, as this can be seen in cases of inflammation, infection, and malignancy. Also, there can be evidence of subdural fluid collections and sagging of brain structures, including cerebellar tonsils. These fluid collections and increased venous blood flow likely occur as compensatory effects to decrease in CSF. MRI brain has identified dura that is thickened and contrast-enhanced and dilation of dural sinuses in several patients with CSF leak or post-LP headache.
Radioisotope cisternography is not commonly used due to less availability but is useful in the setting of spontaneous ICH if a CSF leak is suspected following a non-diagnostic MRI. The test is performed by injection of radioisotope intrathecally via lumbar puncture. It is not typically the best test for identifying the exact site of CSF leak secondary to a dural defect. This is where CT myelography comes into play as it is useful for localizing the level of the spinal leak.
Treatment of intracranial hypotension is related to the underlying cause. In cases of benign ICH and CSF leak, conservative measures are preferred initially, as many patients respond to such without undergoing surgical intervention. Effective therapies include bed rest, good oral hydration, caffeine supplementation, glucocorticoids, mineralocorticoids, and abdominal binders. If conservative measures fail to improve symptoms, more invasive treatment such as lumbar epidural blood patch (EBP) and less commonly, continuous epidural saline infusion and surgical repair of the leak are performed. Epidural blood patches have been found effective in most patients but can recur in days to weeks.
Headache is a common medical complaint. Therefore a headache secondary to ICH can often be confused with more commonly presenting diagnoses such as migraine, tension headache, or meningitis. Other conditions such as subarachnoid hemorrhage, subdural hematoma, over drainage of CSF secondary to a ventricular shunt, arteriovenous malformation, or brain malignancy can present with headache without significant neurological deficits on a physical exam which can make it difficult to distinguish the cause of the headache and make the diagnosis of ICH.
Following diagnosis and treatment for ICH, symptoms commonly resolve spontaneously within two weeks. In rare cases, symptoms have persisted for weeks to months. There is a limited amount of data available to assess the long-term outcomes of patients following ICH diagnosis, but a clinical review of available literature concluded that 10% of patients would have a recurrence of CSF leakage, regardless of treatment modality or course.
Aside from commonly associated symptoms mentioned previously, more serious CNS complications have been correlated to cases of spontaneous ICH. These complications are thought to be secondary to the deformity of CNS structures as a result of compression. These rare manifestations have presented clinically as galactorrhea, hyperprolactinemia, ataxia, quadriparesis, cerebellar hemorrhage, posterior circulation infarction, movement disorders, decreased level of consciousness, and cerebral venous sinus thrombosis.
Patients should be informed about the cause of the symptoms they are experiencing and the course of management. Conservative treatment should be tried for one to two weeks, and activity can be resumed gradually as symptoms improve. Following a trial period of conservative therapy, other courses of treatment should be discussed to provide relief of symptoms. Epidural blood patch (EBP) is an effective next step in treatment, and patients should be aware of the progression to this form of treatment for ICH. The efficacy of EBP in the treatment of spontaneous ICH is lower than for post-dural puncture headache, which should be discussed with patients so that the expectations are realistic as treatment becomes more invasive with persisting symptoms.
In the healthcare system, support staff should be informed of the possible side effects of a procedure of any kind that interrupts the dural space, which can cause a postural headache secondary to ICH. The staff must be aware of the cause of the symptoms, at least on a basic level, so that they may assist in the conservative measures to improve symptoms and enhance the patient outcomes. It is the goal of all members of the healthcare team that the patient has a complete resolution of symptoms. In order to accomplish this, it is integral to have clear communication between physicians, such as anesthesiologists which perform LPs, and the nurses and nurse assistants caring for the patients on an hourly basis. The support staff needs to be made aware of what to look for and how to improve symptoms and prognosis.
|||Mokri B, Spontaneous cerebrospinal fluid leaks: from intracranial hypotension to cerebrospinal fluid hypovolemia--evolution of a concept. Mayo Clinic proceedings. 1999 Nov; [PubMed PMID: 10560599]|
|||Mokri B,Hunter SF,Atkinson JL,Piepgras DG, Orthostatic headaches caused by CSF leak but with normal CSF pressures. Neurology. 1998 Sep; [PubMed PMID: 9748027]|
|||SCHALTENBRAND G, Normal and pathological physiology of the cerebrospinal fluid circulation. Lancet (London, England). 1953 Apr 25; [PubMed PMID: 13036182]|
|||Levine DN,Rapalino O, The pathophysiology of lumbar puncture headache. Journal of the neurological sciences. 2001 Nov 15; [PubMed PMID: 11701146]|
|||Mokri B,Maher CO,Sencakova D, Spontaneous CSF leaks: underlying disorder of connective tissue. Neurology. 2002 Mar 12; [PubMed PMID: 11889250]|
|||Schievink WI,Maya MM,Jean-Pierre S,Nuño M,Prasad RS,Moser FG, A classification system of spontaneous spinal CSF leaks. Neurology. 2016 Aug 16; [PubMed PMID: 27440149]|
|||Kumar N,Diehn FE,Carr CM,Verdoorn JT,Garza I,Luetmer PH,Atkinson JL,Morris JM, Spinal CSF venous fistula: A treatable etiology for CSF leaks in craniospinal hypovolemia. Neurology. 2016 Jun 14; [PubMed PMID: 27178701]|
|||Schievink WI,Schwartz MS,Maya MM,Moser FG,Rozen TD, Lack of causal association between spontaneous intracranial hypotension and cranial cerebrospinal fluid leaks. Journal of neurosurgery. 2012 Apr; [PubMed PMID: 22264184]|
|||Franzini A,Messina G,Nazzi V,Mea E,Leone M,Chiapparini L,Broggi G,Bussone G, Spontaneous intracranial hypotension syndrome: a novel speculative physiopathological hypothesis and a novel patch method in a series of 28 consecutive patients. Journal of neurosurgery. 2010 Feb; [PubMed PMID: 19591547]|
|||Schievink WI, Spontaneous spinal cerebrospinal fluid leaks and intracranial hypotension. JAMA. 2006 May 17; [PubMed PMID: 16705110]|
|||Marcelis J,Silberstein SD, Spontaneous low cerebrospinal fluid pressure headache. Headache. 1990 Mar; [PubMed PMID: 2335473]|
|||Pannullo SC,Reich JB,Krol G,Deck MD,Posner JB, MRI changes in intracranial hypotension. Neurology. 1993 May; [PubMed PMID: 8492946]|
|||Good DC,Ghobrial M, Pathologic changes associated with intracranial hypotension and meningeal enhancement on MRI. Neurology. 1993 Dec; [PubMed PMID: 8255481]|
|||Mokri B,Piepgras DG,Miller GM, Syndrome of orthostatic headaches and diffuse pachymeningeal gadolinium enhancement. Mayo Clinic proceedings. 1997 May; [PubMed PMID: 9146681]|
|||Rando TA,Fishman RA, Spontaneous intracranial hypotension: report of two cases and review of the literature. Neurology. 1992 Mar; [PubMed PMID: 1549206]|
|||Schievink WI,Nuño M,Rozen TD,Maya MM,Mamelak AN,Carmichael J,Bonert VS, Hyperprolactinemia due to spontaneous intracranial hypotension. Journal of neurosurgery. 2015 May; [PubMed PMID: 25380110]|
|||Chi NF,Wang SJ,Lirng JF,Fuh JL, Transtentorial herniation with cerebral infarction and duret haemorrhage in a patient with spontaneous intracranial hypotension. Cephalalgia : an international journal of headache. 2007 Mar; [PubMed PMID: 17381561]|
|||Pleasure SJ,Abosch A,Friedman J,Ko NU,Barbaro N,Dillon W,Fishman RA,Poncelet AN, Spontaneous intracranial hypotension resulting in stupor caused by diencephalic compression. Neurology. 1998 Jun; [PubMed PMID: 9633740]|
|||Zhang D,Wang J,Zhang Q,He F,Hu X, Cerebral Venous Thrombosis in Spontaneous Intracranial Hypotension: A Report on 4 Cases and a Review of the Literature. Headache. 2018 Sep; [PubMed PMID: 30238694]|
|||Schievink WI,Maya MM,Louy C, Cranial MRI predicts outcome of spontaneous intracranial hypotension. Neurology. 2005 Apr 12; [PubMed PMID: 15824366]|