Low CSF pressure headache

Orthostatic headaches following dural puncture are well known to anaesthetists as well as other physicians who perform lumbar punctures. However, due to the progression of medical knowledge and newer diagnostic capabilities, many other causes of low pressure headaches have been recognised. Even though low pressure headache is largely underdiagnosed at present, with increased awareness it may become a common finding in the future. This article includes symptoms, diagnostic problems, and treatment options available for patients with low CSF pressure headache including post dural puncture headaches.


Introduction
The normal intracranial pressure (ICP) depends on age and body posture. In a healthy adult this could range between 7-15mmHg supine to -10 to -15mmHg in vertical position. According to the Monroe-Kellie doctrine, the total intracranial volumes which consist of brain, blood, CSF and other pathological entities such as tumours remain fixed. 1 The dynamics of ICP is maintained by changing volumes of blood or CSF. While cerebral blood flow (CBF) depends on cerebral perfusion pressure (CPP), the CSF production, absorption and circulation play a key role in ICP. 2 Normal production of CSF in an adult is around 500ml a day and its pressure in the lumbar spine could vary between -5 to-15 mmHg on horizontal and around 40mmHg in sitting positions. 3 The most common neurologic symptom associated with CSF pressure change is headache. Low pressure headaches, which are due to low CSF pressure or volume, are increasingly implicated as a cause of daily persistent headache. 1,2,3,4 Low pressure headache could be provoked (following lumbar puncture or breaching of the dura following a neurosurgical procedure) or spontaneous (CSF leak). Low pressure headache without any clear provocation is termed as spontaneous intracranial hypotension (SIH). 5,6,7 Causes of spontaneous and iatrogenic CSF leak (Box 1) Spontaneous CSF leak generally neither present with any local symptoms nor carry any risk of infection, as the CSF leak is into a sterile environment. This is unlike the CSF leak following a surgical procedure or traumatic injury. Causes of the leak are largely unknown but the predisposing dural weakness such as dural or arachnoid diverticula or trivial trauma are hypothesised as contributing factors and are commonly found in patients with connective tissue disorders. 7,8,9 One of the postulated complications of weak dural tissue is possible CSF leak around those areas (nerve root sheath, epidural cyst or diverticula) due to cough, minor trauma or severe exercise or even dural tear caused by a spondylitic spur. 7,8,10,11,12 Anatomical location of the CSF leaks need to be actively investigated on a suspected patient. 4,8,10,12 The commonest anatomical sites are at the cervicothoracic junction or at the thoracic spine. The skull base is the least common place to have CSF leaks. 8,10,11 Iatrogenic CSF leaks in anaesthetic practice mainly occur following lumbar puncture or neurosurgical interventions.

The anatomy and pathophysiology of low pressure headaches
The spinal dura mater starts at the foramen magnum and can extend up to the lower limit of S2 which consist of dense connective tissue matrix of collagen. Nevertheless there are tight fibrous connective tissues being identified connecting the posterior spinal dura at the atlanto -axial and atlanto-occiptal levels to nuchal ligament. 6,13,14  The pathophysiology of the disease was first described by Augustus Bier in the 1890s as being due to a CSF leak. The pain generators of the low pressure headache are not entirely certain. The best theoretical explanation is, that the imbalance between the CSF leak through the dural defect and the production, give rise to depletion of CSF volume. Firstly this will generate reflex vasodilation of pain sensitive cerebral vessels to compensate intra cranial volumes; secondly there will be traction on pain sensitive meninges and cranial and spinal nerves. Furthermore another causative factor of headache is neuronal hypersensitivity to substance P which is released in high quantities in up to 30% of the dural puncture patients.
Clinical presentation and diagnosis of low CSF pressure headache 10 The commonest clinical presentation in low CSF pressure headache is orthostatic headache which occurs or worsens within 15 minutes on upright position and improves within 30min of 'lying down' or within 3 days of epidural blood patches, although this could be variable. 7,8 Iatrogenic low CSF pressure headaches are followed by the event and 66% to 90% dural puncture related CSF leaks become symptomatic in 2 to 3 days respectively. 7 Onset of spontaneous CSF leak headaches could be abrupt or sub-acute, reaching maximum intensity overtime or may be very vague and become apparent over time. [10][11][12][13][14][15] Typically the pain locations are frontal (5 th cranial) occipital, temporal (9 th and 10 th cranial) neck and shoulders (C1, 2, 3). 8,9 Description of headache may be throbbing, or non-throbbing, pulling the head toward the neck, feeling of an ice cube in an empty glass and it is rarely unilateral. 4,8 Although postural headache is the hallmark of low CSF pressure headache, in untreated patients the posture related component may become less prominent. Headache may become lingering and persistent and unrelated to posture or completely absent. 7,8,12,15 The most common accompanying symptoms according to literature reports are nausea, neck stiffness and photophobia which suggest meningeal irritation. The symptoms such as tinnitus and hyperacusis (extreme aversion and hypersensitivity to sounds) or hypoacusia (slightly diminished acuteness of the sense of hearing) with a sense of losing balance are associated with irritation of 8 th intra cranial nerve complex. 4,8,9,12,15 An ophthalmological symptom such as diplopia after spinal anaesthesia was described by Augustus Bier for the first time 100 yrs ago. The ophthalmological effects such as visual blurring or visual field defect and diplopia are due to the effects on 2 nd , 3 rd , 4 th and 6 th cranial nerves. The common and rare clinical manifestations of CSF leak in otherwise healthy adults are summarised in Box 2. Subtle cognitive changes may fail to be recognised until the successful treatment of the CSF leak. Spinal manifestation of the CSF leak can be shoulder, inter scapular pain, radicular symptoms or local back pain at the site of the injections. 8,9,12,15 As with any other disease, diagnosis should start with listening to the patient's history and a thorough examination. Low pressure nature could be easily missed as the presentation symptoms could be vague, especially in spontaneous CSF leak, however such patients may also present with acute symptoms. 16 Although 90% of PDPH patients present within first 3 days, presentation could be delayed up to 12 days or if untreated headache can remain with long term CSF leak. 17,18,19,20 Box 2: Common and rare clinical manifestation of CSF leaks 10,15 (These symptoms have been reflected in the International Headache Society (IHS) Diagnostic Criteria (Box 3) caused by low ICP. 4,5,8 ) If the clinical diagnosis of CSF leak has been suspected, radiological investigation and diagnostic studies will greatly facilitate the confirmation of the cause as well as its anatomical location. Magnetic Resonance Imaging (MRI) has greatly improved the understanding of the features of intracranial hypotension as well as reduces the time needed to confirm the diagnosis. (Figure 1) On the other hand poor understanding of the MRI changes or variable findings, may prevent the patient been diagnosed with low pressure headache. Diagnostic studies and typical features seen are summarised in Box 4.

Box 4: Diagnostic studies
If the clinical diagnosis of CSF leak has been suspected, radiological investigation and diagnostic studies will greatly facilitate the confirmation of the cause as well as its anatomical location. Magnetic Resonance Imaging (MRI) has greatly improved the understanding of the features of intracranial hypotension as well as reduces the time needed to confirm the diagnosis. (Figure 1) On the other hand poor understanding of the MRI changes or variable findings, may prevent the patient been diagnosed with low pressure headache. Diagnostic studies and typical features seen are summarised in Box 4. Incidence and differential diagnosis (Box 5) Low pressure headaches associated with spontaneous intracranial hypotension and fistula leaks are rare (5 in 100,000, female to male ratio 1:2). On the other hand incidence in post dural puncture headache (PDPH) is not uncommon and could vary (10-30%). 2,8,20,21,22 Diagnostic study In the presence of extradural fluid will helpful to identify the location of the leak, but this is very rare to be effective.

Conservative treatment
Patients who seek medical treatment should initially be treated with conservative methods.
The key is to reassure the patient and provide emotional support, bed rest, regular analgesics and hydration. Even though bed rest has been advocated it can only postpone the headache in some PDPH patients. Oral and intravenous hydration remain key to avoid dehydration, as poor hydration is associated with headaches, although it has not shown to increase the CSF production. 7,8,9 Caffeine Effect of caffeine is due to cerebral vasoconstriction and stimulating the CSF production. Intravenous injection of caffeine may be 70 to 80% effective in the initial stage of the treatment of PDPH, but unfortunately headache may return after 48 hours. 7,9,11 Theophylline As with caffeine intravenous theophylline causes cerebral vasoconstriction.

Adrenocorticotropic hormones
Steroid hormones act by stimulating adrenal gland to increase CSF production and endorphin release, and can be used to treat low CSF pressure headaches.
Epidural saline and colloid infusions These methods only produce transient effect due to increase in epidural pressure thereby reducing the CSF leak temporarily.
Autologous epidural blood patch (ABP) In the event of failure to respond to conservative treatment using a targeted epidural blood patch should be considered. The main stay of treatment of CSF leak with autologous epidural blood (ABP) patch was first described by Gromeley in 1960. 21 Pain relief is usually instantaneous and this often confirms the diagnosis. The mechanism of pain relief is firstly associated with the immediate dural tamponade effect and secondly with sealing of the dural leak. The success rate of persistent pain relief in PDPH could vary between 61 to 95%. Most recommended blood volumes are 15 to 20ml for the 1 st blood patch. A second ABP will be able to relieve symptoms in almost all patients. 7 On the other hand in spontaneous intracranial hypotension, ABP may help only up to 30% of the patients. 7,8 The discrepancy is likely to be due to the fact that spontaneous leaks could also be in the anterior aspect of the dura, the dural sleeves or could be due to multiple leaks. Furthermore dural holes may be complicated with weak unsupported subarachnoid tissues. In the event of multiple leaks, targeted multiple limited EBP could be performed at multiple sites. 11 If the 1 st ABP is not effective the second blood patch with up to 100ml could be injected within 5 days interval. The volume of blood could be restricted due to high risk of infection with large volumes as well as back and radicular pain. 8,22 Other techniques If epidural blood patching fails to reduce pain, placement of percutaneous fibrin sealant should be performed. Surgical repair should be left as the last resort for patients who are refractory to all other methods of treatment. Surgical repair of the CSF leaks are safe and can provide long lasting relief but this needs knowledge of the precise anatomical location of the leak. Accurate diagnosis and treatment of the low CSF pressure headache has very good prognosis of long lasting relief with less than 10% of recurrence in spontaneous CSF leaks. 8 In conclusion, low CSF pressure headaches while not a life threatening condition may cause considerable lowering of the quality of life. Iatrogenic causes of low CSF pressure headaches are well recognised and measures to reduce it should be undertaken. Spontaneous intracranial hypotension often remains under diagnosed. The spectrum of clinical and radiographic manifestations is varied, with diagnosis largely based on clinical suspicion, cranial magnetic resonance imaging, and myelography. Numerous treatment options are available, but much remains to be learned about this disorder.