High- and Low-Pressure Headache

Educational Objectives

The goal of this program is to improve management of intracranial hypertension and hypotension. After hearing and assimilating this program, the clinician will be better able to:

1. Identify risk factors for idiopathic intracranial hypertension and spontaneous intracranial hypotension.
2. Perform a diagnostic workup for idiopathic intracranial hypertension and spontaneous intracranial hypotension.
3. Treat headache symptoms associated with idiopathic intracranial hypertension and spontaneous intracranial hypotension.
4. Differentiate idiopathic intracranial hypertension and spontaneous intracranial hypotension from other headache etiologies.

Summary

Pseudotumor Cerebri Syndrome (Idiopathic Intracranial Hypertension [IIH])

Diagnostic criteria: definite diagnosis can be made if the patient has papilledema with a normal neurologic examination (with the exception of cranial nerve abnormalities) and neuroimaging (except for signs of high pressure); magnetic resonance imaging (MRI) of the brain and magnetic resonance venography are ideal (computed tomography [CT] with contrast can be performed if MRI is contraindicated); lumbar puncture is essential to confirm the diagnosis, and opening cerebrospinal fluid (CSF) pressure of ≥250 mm H₂O in adults and ≥280 mm H₂O in children are diagnostic (≥250 mm H₂O in nonobese, non-sedated children)

Epidemiology: primarily affects overweight women of childbearing age; overall incidence is 5 per 100,000 individuals and 25 per 100,000 overweight women of childbearing age; new presentation is rare among patients >45 yr of age

Randomized trial of acetazolamide vs placebo: acetazolamide doses were increased from 1000 mg/day to 4000 mg/day if tolerated; all patients had access to a supervised dietary program; primary outcome was the change in perimetric mean deviation (measure of visual field function) at 6 mo; compared with the placebo group, the acetazolamide group had greater improvement in perimetric mean deviation, papilledema grade, visual quality of life, weight reduction, and CSF pressure, and similar improvement in headache disability

Headache: frequency — most common symptom; reported in 84% of patients and was the initial symptom in 35%; characteristics — resembled migraine without aura or tension-type headache; many patients reported unilateral headaches; concomitant neck pain was common; daily pain was reported in 25% of patients, and 42% of patients reported being awakened by pain; associated with severe disability, with an average Headache Impact Test-6 (HIT-6) score of 60; 41% of patients with headache had a history of migraines; HIT-6 scores were not correlated with opening pressure, body mass index, papilledema grade, visual measurements, treatment type, use of hormonal contraceptives, or history of polycystic ovary syndrome, anxiety, or depression; causes — possibly related to changes in the venous system of the brain, venous sinus stenosis, or central sensitization

Other symptoms: included transient visual obscurations (70% of patients); pulsatile or nonpulsatile tinnitus; subjective vision loss; diplopia; neck, back, and radicular pain, muscular pain remote from the head; dizziness; poor balance; depression; and systemic fluid retention

Papilledema: graded using the Frisén scale; hemorrhages, exudates, and cotton-wool spots are not considered in grading; swelling of the nerve is unlikely to occur once optic atrophy and disk pallor develop due to loss of nerve fibers (thus, it is not an accurate sign of progression)

Visual acuity: poor indicator of disease progression; central vision tends to be affected in the late stages

Ocular motility: may be normal, but patients may have a unilateral or bilateral palsy of cranial nerve VI; generalized limitation of eye movements warrants further investigation of potential secondary causes

Visual field: automated perimetry is helpful for diagnosis and monitoring of papilledema; enlargement of the physiologic blind spot, defects of the arcuate field, and generalized constriction increase suspicion

Diagnosis:history — inquire about recent weight gain and assess obesity status; potential secondary causes include recent use of vitamin A, tretinoin, or tetracycline antibiotics; multiple conditions, eg, venous sinus thrombosis, have been associated with IIH; lumbar puncture — essential for diagnosis; opening pressure should be measured with the patient in the lateral decubitus position, and the quantity of CSF removed should be sufficient to put the closing pressure in the mid-normal range; weight is not correlated with opening pressure; MRI — imaging of the brain and orbits is recommended; MRV — recommended to exclude thrombosis and view venous sinuses; evaluation for sleep apnea — recommended if the patient is at high risk; factors that influence opening pressure — include patient position, sedation, Valsalva maneuver, and medications (including acetazolamide); neuroimaging abnormalities — may include increased diameter of subarachnoid space, swelling of optic nerve, flattening of the back of the globe, expanded or empty sella, and cerebellar tonsillar descent; results of a study of patients with IIH or isolated pulsatile tinnitus who were undergoing placement of a lateral stent suggested that empty sella may be related to venous sinus stenosis rather than intracranial hypertension

Study of MRI findings and diagnosis of IIH: patients who underwent MRI of the brain and had photographs of the fundus were evaluated; most common reason for MRI was a history of brain tumor (8.8% of patients underwent MRI for headaches); 49% of patients had one or more findings on MRI, with an empty sella identified in ≈33%; the 5 patients who had papilledema had a history of IIH or a high body mass index, and they had a higher prevalence of an empty sella, optic nerve tortuosity, and stenosis of the transverse venous sinus; prevalence of papilledema increased from 2.8% among patients with one sign to 40% among those with 4 signs; results indicate that MRI findings suggestive of IIH were common but are rarely associated with papilledema; management of incidental findings requires clinical correlation

Goals for management: treatment may not be required, eg, if patient is asymptomatic; goal of treatment is to preserve vision, treat underlying disease, and minimize headache morbidity; patient should be managed by neuro-ophthalmology or co-managed by ophthalmology and neurology

Medical management: all treatments are off-label; acetazolamide is usually the first choice for treatment and works by decreasing secretion of CSF from the choroid plexus; methazolamide is considered the second choice and is better tolerated than acetazolamide (but is often difficult to access); furosemide or bumetanide may be considered; triamterene, spironolactone, or ethacrynic acid may be substituted in patients who are allergic to sulfonamides; allergies to sulfonamide-based antibiotics do not preclude patients from taking sulfonamide-based diuretics

Headaches: based on type of headache (eg, migraine or tension); topiramate is effective and may aid with weight loss, although not all patients can tolerate it; studies on calcitonin gene-related peptide monoclonal antibodies show conflicting results; therapies that have minimal side effects, eg, weight gain and fluid retention, are preferred; valproate, verapamil, steroids, opioids, and butalbital should be avoided when possible

Surgical management: optic nerve sheath fenestration (ONSF) — generally reserved for patients with papilledema and vision loss; relapse is possible; shunting — ventriculoperitoneal shunting is more effective and has better long-term results than lumboperitoneal shunting; headaches may improve initially but generally return ≤3 yr; revision rate is high; generally reserved for patients at high risk for significant vision loss; stenting — decreases gradient of pressure across transverse sinuses; look for smooth-walled stenosis or filling defects on CT venography or MR venography; study showed that higher gradients were associated with better outcomes

Pediatric patients: no predilection for either sex before puberty; after puberty, teenage girls may be at increased risk for vision loss; secondary causes, eg, medications or lateral sinus stenosis after ear infection, are common; treatment is same as for adults

Pregnancy: becoming pregnant and use of hormonal contraceptives are not contraindicated for patients with a history of IIH, and risk for development of IIH is not increased during pregnancy; repeated lumbar puncture and acetazolamide are acceptable (preferably after the first trimester for acetazolamide); topiramate should be avoided during pregnancy; surgery or steroids may be administered; risks for fetal loss or complications during delivery are not increased

Fulminant variants: require aggressive medical and surgical management to prevent blindness; secondary causes should be investigated

Prognostic factors: vision loss at presentation (visual field or acuity), uncontrolled systemic hypertension, profound anemia, renal failure, and venous sinus thrombosis were associated with poor outcomes; in the speaker’s study, patients with high-grade papilledema, optic disc hemorrhages, and decreased acuity at baseline, and those randomized to receive placebo had worse outcomes; psychiatric disorders (eg, major depression) have been reported as a poor prognostic feature

Diagnosis without papilledema: possible if the patient has a sixth nerve palsy or ≥3 findings on MRI (empty sella, flattening of posterior sclera, distention of perioptic subarachnoid space, or stenosis of the transverse venous sinus)

Take-home messages: rule out other causes in overweight women of childbearing age with headaches (do not assume diagnosis); ophthalmoscopy and visual testing are not mandatory for diagnosis; treatments are based on visual status; headaches may require separate treatment from elevated pressure; patients with high pressure can develop low pressure

Spontaneous Intracranial Hypotension (SIH)

Overview: condition is not always spontaneous, the cause may not be located intracranially, and blood and CSF pressures may be normal; arises from a spinal leak secondary to a dural defect; extravasation may occur in the epidural space or in an adjacent vein (CSF-venous fistula); typically develops in the low cervical or thoracic horn; symptoms do not arise from cranial CSF leaks

Incidence and risk factors: incidence — appears to be more common in women; peak incidence is ≈40 yr of age (although it can occur at any age); annual incidence is ≥5 per 100,000 individuals; patients may go undiagnosed for several years; risk factors — include joint hypermobility (eg, Ehlers-Danlos syndrome), trauma, spinal procedures (including lumbar puncture), disc disease, and history of spontaneous retinal detachment

Headache features: may not be present, but SIH should be suspected in patients who develop new and persistent daily headaches; may start as a thunderclap headache and can be located anywhere; may be accompanied by facial, neck, or upper back pain; may be orthostatic and worsen toward the end of the day, although the positional component may decrease over time; typically worsened by physical exertion or Valsalva maneuvers and often improves at high altitudes

Other symptoms: include vestibulocochlear symptoms, ringing or pulsatile tinnitus, hearing loss, poor balance, spinal symptoms, neck pain, pain between the shoulder blades, chest pain, and pain on the side of the leak; visual symptoms are less common than with high-pressure headaches but may include diplopia, blurred vision, and visual field defects; other reported symptoms include facial pain, facial palsy, movement disorders (eg, chorea or tremor), cognitive dysfunction (very common), coma, galactorrhea, subdural fluid collection (nontraumatic subdural hematoma is considered to be SIH until proven otherwise), intracranial hemorrhage, altered taste or smell, and difficulty swallowing; any cranial nerve may be involved

Diagnosis: spontaneous venous pulsation in the retina may be present but cannot be used alone as a diagnostic sign; may be helpful to place the patient in the Trendelenburg position for 5 to 10 min to see if symptoms improve; assessment of joint hypermobility and inquiry about current and past flexibility are recommended; MRI with gadolinium is abnormal in ≈75% of cases; MRI of the brain with contrast should be performed; subarachnoid hemorrhage and superficial siderosis may occur but are uncommon; spinal imaging with CT myelography, MRI with heavily T2-weighted imaging, or digital subtraction myelography should be performed; radionuclide cisternography is expensive and generally not useful; lumbar puncture should be avoided and can worsen SIH

Management: conservative strategies — include consumption of caffeine and use of abdominal binders or compression garments to increase venous pressure; elevating the foot of the bed or using inversion tables can alleviate symptoms; adequate hydration, increasing salt intake, analgesics, steroids, and greater occipital nerve blocks may be helpful; epidural blood patch — start with a high-volume epidural blood patch if MRI of the brain is normal; success rate is 30% to 40%; if MRI is abnormal, look for the site of leakage using CT myelography, and targeted blood patches may be administered using fibrin glue or sealant after identification of the site of the leak; digital subtraction myelography is recommended if results are unsatisfactory

Prognosis: condition is disabling and requires repeated diagnostic and therapeutic procedures; patients with joint hypermobility may be prone to developing additional leaks; rebound hypertension can occur after therapeutic procedures and may require treatment

Take-home messages: site of leakage is often not located; patients should be referred to an imaging center that has specific protocols to detect leaks

Readings

Ansel S et al. Efficacy of epidural blood patches for spontaneous low-pressure headaches: a case series. J R Coll Physicians Edinb. 2016 Dec;46(4):234-237; Avery RA. Reference range of cerebrospinal fluid opening pressure in children: historical overview and current data. Neuropediatrics. 2014 Aug;45(4):206-211; Friedman DI. Headaches due to low and high intracranial pressure. Continuum (Minneap Minn). 2018 Aug;24(4, Headache):1066-1091; Friedman DI et al. Headache in idiopathic intracranial hypertension: findings from the Idiopathic Intracranial Hypertension Treatment Trial. Headache. 2017 Sep;57(8):1195-1205; Friedman DI et al. Revised diagnostic criteria for the pseudotumor cerebri syndrome in adults and children. Neurology. 2013 Sep;81(13):1159-1165; Fuino R et al. Spontaneous intracranial hypotension caused by thoracic disc disease. Headache. 2020 Sep;60(8):1830-1831; Liu FC et al. Connective tissue disorders in patients with spontaneous intracranial hypotension. Cephalalgia. 2011 Apr;31(6):691-695; Park DSJ et al. Idiopathic intracranial hypertension in pregnancy [published online ahead of print, 2021 Jan 4]. J Obstet Gynaecol Can. 2021 Jan;S1701-2163(20)31041-0; Sinclair AJ et al. Rating papilloedema: an evaluation of the Frisén classification in idiopathic intracranial hypertension. J Neurol. 2012 Jul;259(7):1406-1412; Smith SV, Friedman DI. The Idiopathic Intracranial Hypertension Treatment Trial: a review of the outcomes [published correction appears in Headache. 2018 Nov;58(10):1697]. Headache. 2017 Sep;57(8):1303-1310; Spitze A et al. Controversies: optic nerve sheath fenestration versus shunt placement for the treatment of idiopathic intracranial hypertension. Indian J Ophthalmol. 2014 Oct;62(10):1015-1021; Thurtell MJ, Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri): recognition, treatment, and ongoing management. Curr Treat Options Neurol. 2013 Feb;15(1):1-12; Wall M et al. Effect of acetazolamide on visual function in patients with idiopathic intracranial hypertension and mild visual loss: the idiopathic intracranial hypertension treatment trial. JAMA. 2014 Apr;311(16):1641-1651; Yiangou A et al. Calcitonin gene related peptide monoclonal antibody treats headache in patients with active idiopathic intracranial hypertension. J Headache Pain. 2020 Sep;21(1):116; Zetchi A, Labeyrie MA, Nicolini E, et al. Empty sella is a sign of symptomatic lateral sinus stenosis and not intracranial hypertension. AJNR Am J Neuroradiol. 2019 Oct;40(10):1695-1700.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, the following has been disclosed: Dr. Friedman is on advisory boards for Alder BioPharmaceuticals, Allergan, Amgen, Avanir Pharmaceuticals, Biohaven Pharmaceuticals, electroCore, Eli Lilly, Impel, Promius, Revance, Supernus, Teva, Theranica, and Zosano; was a clinical trial site principal investigator for Allergan, Eli Lilly, and Zosano; was a consultant for Avanir, Autonomic Technologies, Eli Lilly, electroCore, and Teva; and received grant/research support from Merck. The planning committee reported nothing to disclose. In her lecture, Dr. Friedman presents information that is related to the off-label or investigational use of a therapy, product, or device.

Acknowledgements

Dr. Friedman was recorded at Headache Update 2021, held July 15-18, 2021, in Lake Buena Vista, FL, and presented by the Diamond Headache Clinic Research and Educational Foundation. For information about upcoming CME conferences from this presenter, please visit dhc-fdn.org. Audio Digest thanks the speakers and meeting presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

OP592301

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.