Idiopathic Intracranial Hypertension Medication
- Author: Mark S Gans, MD; Chief Editor: Andrew G Lee, MD more...
Specific therapy for idiopathic intracranial hypertension (IIH) is aimed at lowering intracranial pressure (ICP) pharmacologically. Carbonic anhydrase inhibitors (eg, acetazolamide) and loop diuretics (eg, furosemide) are thought to exert their effect on ICP by reducing cerebrospinal fluid (CSF) production at the choroid plexus. Cardiac glycosides have a similar effect.
Corticosteroids are indicated on a short-term basis in patients who present with severe papilledema and compromise of their visual function. They are effective in reducing ICP, but the mechanism of action is unknown. Corticosteroids are often used as maximum medical management when rapid lowering of ICP is required.
Patients with IIH may experience headaches that have many of the features of migraine. These headaches can often be controlled with amitriptyline, propranolol, or other commonly prescribed migraine prophylaxis agents. Topiramate is also an excellent choice, in that one of its side effects is weight loss (a common association in IIH), which can help put the disease in remission.
Antiglaucoma, Carbonic Anhydrase Inhibitors
Carbonic anhydrase (CA) is an enzyme found in many tissues. It catalyzes a reversible reaction whereby carbon dioxide becomes hydrated and carbonic acid becomes dehydrated. These changes may result in a decrease in CSF production by the choroid plexus.
Acetazolamide is a nonbacteriostatic sulfonamide and a potent CA inhibitor that is effective in diminishing fluid secretion. It lowers ICP by decreasing production of CSF. Inhibition of CA results in a drop in sodium ion transport across the choroidal epithelium. Reduction of CSF production occurs within hours.
Acetazolamide commonly achieves long-lasting control of transient visual obscurations, headache, and diplopia, all of which are manifestations of intracranial hypertension, even though papilledema does not resolve completely. The effect on ICP is not sustained, and many patients develop adverse effects severe enough to hinder compliance.
Few patients tolerate dosages higher than 2 g/day, but 4 g/day may be required to produce a measurable pressure-lowering effect. Treatment is usually initiated at 1 g/day and increased to 2 g/day if symptoms are not controlled and adverse effects are not severe. Treatment with acetazolamide alone is not appropriate for patients who are experiencing progressive visual field loss.
Loop diuretics inhibit reabsorption of sodium in the ascending limb of the loop of Henle and have a weak inhibitory action on CA.
Furosemide inhibits CSF production, but the precise mechanism by which it does so is unclear. A combination of CA inhibition and an effect on sodium absorption across the choroid plexus may result in the decreased CSF production.
Cardiac glycosides reduce CSF production at choroid plexus and reduce ICP.
Digoxin is present in high concentrations in the choroid plexuses of patients taking standard cardiac doses. It has been shown to reduce CSF production by as much as 78% in humans, probably by inhibiting the Na-K-ATPase pump. There has been only 1 report in which a patient with IIH was treated with digoxin, but the patient was asymptomatic, and thus, it is not known whether symptoms would have been controlled.
Glucocorticoids reduce ICP through an unknown mechanism.
The mechanism of action by which corticosteroids lower CSF pressure has not been established. Some believe that they may facilitate outflow at arachnoid granulations.
The mechanism of action by which corticosteroids lower CSF pressure has not been established. Some believe that they may facilitate outflow at arachnoid granulations.
Beta-blockers may prevent migraines by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues. Significant to their activity as migraine prophylactic agents is the lack of partial agonistic activity. Latency from initial treatment to therapeutic results may be as long as 2 months.
Propranolol is FDA approved for migraine prophylaxis.
Amitriptyline, nortriptyline, doxepin, and protriptyline have been used for migraine prophylaxis, but only amitriptyline has proven efficacy and appears to exert its antimigraine effect independent of its effect on depression.
Amitriptyline has efficacy for migraine prophylaxis that is independent of its antidepressant effect. Its mechanism of action is unknown, but it inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.
These drugs are effective in prophylaxis of migraine headache.
Topiramate is indicated for migraine headache prophylaxis. Its precise mechanism of action is unknown, but the following properties may contribute to its efficacy: (1) blockage of voltage-dependent sodium channels, (2) augmentation of activity of the neurotransmitter GABA at some GABA-A receptor subtypes, (3) antagonization of the AMPA/kainate subtype of the glutamate receptor, and (4) inhibition of the carbonic anhydrase enzyme, particularly isozymes II and IV. Topiramate is also an excellent choice, in that one of its side effects is weight loss (a common association in IIH), which can help put the disease in remission.
Divalproex is now considered first-line preventive medication for migraine. This agent is believed to enhance GABA neurotransmission, which may suppress events related to migraine that occur in cortex, perivascular sympathetics, or trigeminal nucleus caudalis. Divalproex has been shown to reduce migraine frequency by 50%.
Gabapentin is used for migraine headache prophylaxis. It has shown efficacy in migraine and transformed migraine.
Jindal M, Hiam L, Raman A, Rejali D. Idiopathic intracranial hypertension in otolaryngology. Eur Arch Otorhinolaryngol. 2009 Jun. 266(6):803-6. [Medline].
Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep. 2008 Mar. 8(2):87-93. [Medline].
Feldon SE. Visual outcomes comparing surgical techniques for management of severe idiopathic intracranial hypertension. Neurosurg Focus. 2007. 23(5):E6. [Medline].
Friedman DI, Jacobson DM. Idiopathic intracranial hypertension. J Neuroophthalmol. 2004 Jun. 24(2):138-45. [Medline].
Friedman DI, Jacobson DM. Diagnostic criteria for idiopathic intracranial hypertension. Neurology. 2002 Nov 26. 59(10):1492-5. [Medline].
Miller NR, Newman NJ. Pseudotumor cerebri (benign intracranial hypertension). In:. Walsh and Hoyt’s Clinical Neuro-Ophthalmology. Vol 1. 5th ed. 1999:523-38.:
Bateman GA, Stevens SA, Stimpson J. A mathematical model of idiopathic intracranial hypertension incorporating increased arterial inflow and variable venous outflow collapsibility. J Neurosurg. 2009 Mar. 110(3):446-56. [Medline].
Farb RI, Vanek I, Scott JN, Mikulis DJ, Willinsky RA, Tomlinson G, et al. Idiopathic intracranial hypertension: the prevalence and morphology of sinovenous stenosis. Neurology. 2003 May 13. 60(9):1418-24. [Medline].
Bateman GA. Association between arterial inflow and venous outflow in idiopathic and secondary intracranial hypertension. J Clin Neurosci. 2006 Jun. 13(5):550-6; discussion 557. [Medline].
Bateman GA. Arterial inflow and venous outflow in idiopathic intracranial hypertension associated with venous outflow stenoses. J Clin Neurosci. 2008 Apr. 15(4):402-8. [Medline].
Corbett JJ. The first Jacobson Lecture. Familial idiopathic intracranial hypertension. J Neuroophthalmol. 2008 Dec. 28(4):337-47. [Medline].
Daniels AB, Liu GT, Volpe NJ, Galetta SL, Moster ML, Newman NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007 Apr. 143(4):635-41. [Medline].
Radhakrishnan K, Ahlskog JE, Garrity JA, Kurland LT. Idiopathic intracranial hypertension. Mayo Clin Proc. 1994 Feb. 69(2):169-80. [Medline].
Rogers AH, Rogers GL, Bremer DL, McGregor ML. Pseudotumor cerebri in children receiving recombinant human growth hormone. Ophthalmology. 1999 Jun. 106(6):1186-9; discussion 1189-90. [Medline].
Crock PA, McKenzie JD, Nicoll AM, Howard NJ, Cutfield W, Shield LK, et al. Benign intracranial hypertension and recombinant growth hormone therapy in Australia and New Zealand. Acta Paediatr. 1998 Apr. 87(4):381-6. [Medline].
Williams JB. Adverse effects of thyroid hormones. Drugs Aging. 1997 Dec. 11(6):460-9. [Medline].
Raghavan S, DiMartino-Nardi J, Saenger P, Linder B. Pseudotumor cerebri in an infant after L-thyroxine therapy for transient neonatal hypothyroidism. J Pediatr. 1997 Mar. 130(3):478-80. [Medline].
Sacchi S, Russo D, Avvisati G, Dastoli G, Lazzarino M, Pelicci PG, et al. All-trans retinoic acid in hematological malignancies, an update. GER (Gruppo Ematologico Retinoidi). Haematologica. 1997 Jan-Feb. 82(1):106-21. [Medline].
Visani G, Bontempo G, Manfroi S, Pazzaglia A, D'Alessandro R, Tura S. All-trans-retinoic acid and pseudotumor cerebri in a young adult with acute promyelocytic leukemia: a possible disease association. Haematologica. 1996 Mar-Apr. 81(2):152-4. [Medline].
Selleri C, Pane F, Notaro R, Catalano L, Santoro LE, Luciano L, et al. All-trans-retinoic acid (ATRA) responsive skin relapses of acute promyelocytic leukaemia followed by ATRA-induced pseudotumour cerebri. Br J Haematol. 1996 Mar. 92(4):937-40. [Medline].
Ahmad S. Amiodarone and reversible benign intracranial hypertension. Cardiology. 1996 Jan-Feb. 87(1):90. [Medline].
Varadi G, Lossos A, Or R, Kapelushnik J, Nagler A. Successful allogeneic bone marrow transplantation in a patient with ATRA-induced pseudotumor cerebri. Am J Hematol. 1995 Oct. 50(2):147-8. [Medline].
Sivin I. Serious adverse events in Norplant users reported to the Food and Drug Administration's MedWatch Spontaneous Reporting System. Obstet Gynecol. 1995 Aug. 86(2):318-20. [Medline].
Baqui AH, de Francisco A, Arifeen SE, Siddique AK, Sack RB. Bulging fontanelle after supplementation with 25,000 IU of vitamin A in infancy using immunization contacts. Acta Paediatr. 1995 Aug. 84(8):863-6. [Medline].
Alder JB, Fraunfelder FT, Edwards R. Levonorgestrel implants and intracranial hypertension. N Engl J Med. 1995 Jun 22. 332(25):1720-1. [Medline].
Malozowski S, Tanner LA, Wysowski DK, Fleming GA, Stadel BV. Benign intracranial hypertension in children with growth hormone deficiency treated with growth hormone. J Pediatr. 1995 Jun. 126(6):996-9. [Medline].
Campos SP, Olitsky S. Idiopathic intracranial hypertension after L-thyroxine therapy for acquired primary hypothyroidism. Clin Pediatr (Phila). 1995 Jun. 34(6):334-7. [Medline].
Nasr SZ, Schaffert D. Symptomatic increase in intracranial pressure following pancreatic enzyme replacement therapy for cystic fibrosis. Pediatr Pulmonol. 1995 Jun. 19(6):396-7. [Medline].
Price DA, Clayton PE, Lloyd IC. Benign intracranial hypertension induced by growth hormone treatment. Lancet. 1995 Feb 18. 345(8947):458-9. [Medline].
Kelly SJ, O'Donnell T, Fleming JC, Einhaus S. Pseudotumor cerebri associated with lithium use in an 11-year-old boy. J AAPOS. 2009 Apr. 13(2):204-6. [Medline].
Mollan SP, Ball AK, Sinclair AJ, Madill SA, Clarke CE, Jacks AS, et al. Idiopathic intracranial hypertension associated with iron deficiency anaemia: a lesson for management. Eur Neurol. 2009. 62(2):105-8. [Medline].
Lin A, Foroozan R, Danesh-Meyer HV, De Salvo G, Savino PJ, Sergott RC. Occurrence of cerebral venous sinus thrombosis in patients with presumed idiopathic intracranial hypertension. Ophthalmology. 2006 Dec. 113(12):2281-4. [Medline].
Kesler A, Yatziv Y, Shapira I, Berliner S, Assayag EB. Increased red blood cell aggregation in patients with idiopathic intracranial hypertension. A hitherto unexplored pathophysiological pathway. Thromb Haemost. 2006 Oct. 96(4):483-7. [Medline].
Warner JE, Larson AJ, Bhosale P, Digre KB, Henley C, Alder SC, et al. Retinol-binding protein and retinol analysis in cerebrospinal fluid and serum of patients with and without idiopathic intracranial hypertension. J Neuroophthalmol. 2007 Dec. 27(4):258-62. [Medline].
Fraser JA, Bruce BB, Rucker J, Fraser LA, Atkins EJ, Newman NJ, et al. Risk factors for idiopathic intracranial hypertension in men: a case-control study. J Neurol Sci. 2010 Mar 15. 290(1-2):86-9. [Medline]. [Full Text].
Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988 Aug. 45(8):875-7. [Medline].
Radhakrishnan K, Ahlskog JE, Cross SA, Kurland LT, O'Fallon WM. Idiopathic intracranial hypertension (pseudotumor cerebri). Descriptive epidemiology in Rochester, Minn, 1976 to 1990. Arch Neurol. 1993 Jan. 50(1):78-80. [Medline].
Radhakrishnan K, Thacker AK, Bohlaga NH, Maloo JC, Gerryo SE. Epidemiology of idiopathic intracranial hypertension: a prospective and case-control study. J Neurol Sci. 1993 May. 116(1):18-28. [Medline].
Digre KB, Nakamoto BK, Warner JE, Langeberg WJ, Baggaley SK, Katz BJ. A comparison of idiopathic intracranial hypertension with and without papilledema. Headache. 2009 Feb. 49(2):185-93. [Medline].
Corbett JJ, Savino PJ, Thompson HS, Kansu T, Schatz NJ, Orr LS, et al. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol. 1982 Aug. 39(8):461-74. [Medline].
Agostoni E, Aliprandi A. Alterations in the cerebral venous circulation as a cause of headache. Neurol Sci. 2009 May. 30 Suppl 1:S7-10. [Medline].
Ney JJ, Volpe NJ, Liu GT, Balcer LJ, Moster ML, Galetta SL. Functional visual loss in idiopathic intracranial hypertension. Ophthalmology. 2009 Sep. 116(9):1808-1813.e1. [Medline].
Wall M, George D. Visual loss in pseudotumor cerebri. Incidence and defects related to visual field strategy. Arch Neurol. 1987 Feb. 44(2):170-5. [Medline].
Shah VA, Kardon RH, Lee AG, Corbett JJ, Wall M. Long-term follow-up of idiopathic intracranial hypertension: the Iowa experience. Neurology. 2008 Feb 19. 70(8):634-40. [Medline].
Kupersmith MJ, Gamell L, Turbin R, Peck V, Spiegel P, Wall M. Effects of weight loss on the course of idiopathic intracranial hypertension in women. Neurology. 1998 Apr. 50(4):1094-8. [Medline].
Rowe FJ, Sarkies NJ. Assessment of visual function in idiopathic intracranial hypertension: a prospective study. Eye (Lond). 1998. 12 ( Pt 1):111-8. [Medline].
Sugerman HJ, Felton WL 3rd, Salvant JB Jr, Sismanis A, Kellum JM. Effects of surgically induced weight loss on idiopathic intracranial hypertension in morbid obesity. Neurology. 1995 Sep. 45(9):1655-9. [Medline].
Sugerman HJ, Felton WL 3rd, Sismanis A, Kellum JM, DeMaria EJ, Sugerman EL. Gastric surgery for pseudotumor cerebri associated with severe obesity. Ann Surg. 1999 May. 229(5):634-40; discussion 640-2. [Medline]. [Full Text].
González-Hernández A, Fabre-Pi O, Díaz-Nicolás S, López-Fernández JC, López-Veloso C, Jiménez-Mateos A. [Headache in idiopathic intracranial hypertension]. Rev Neurol. 2009 Jul 1-15. 49(1):17-20. [Medline].
Nampoory MR, Johny KV, Gupta RK, Constandi JN, Nair MP, al-Muzeiri I. Treatable intracranial hypertension in patients with lupus nephritis. Lupus. 1997. 6(7):597-602. [Medline].
Leker RR, Steiner I. Anticardiolipin antibodies are frequently present in patients with idiopathic intracranial hypertension. Arch Neurol. 1998 Jun. 55(6):817-20. [Medline].
Sussman J, Leach M, Greaves M, Malia R, Davies-Jones GA. Potentially prothrombotic abnormalities of coagulation in benign intracranial hypertension. J Neurol Neurosurg Psychiatry. 1997 Mar. 62(3):229-33. [Medline]. [Full Text].
Bachman DT, Srivastava G. Emergency department presentations of Lyme disease in children. Pediatr Emerg Care. 1998 Oct. 14(5):356-61. [Medline].
Agid R, Farb RI, Willinsky RA, Mikulis DJ, Tomlinson G. Idiopathic intracranial hypertension: the validity of cross-sectional neuroimaging signs. Neuroradiology. 2006 Aug. 48(8):521-7. [Medline].
Maralani PJ, Hassanlou M, Torres C, Chakraborty S, Kingstone M, Patel V, et al. Accuracy of brain imaging in the diagnosis of idiopathic intracranial hypertension. Clin Radiol. 2012 Jul. 67(7):656-63. [Medline].
Stone MB. Ultrasound diagnosis of papilledema and increased intracranial pressure in pseudotumor cerebri. Am J Emerg Med. 2009 Mar. 27(3):376.e1-376.e2. [Medline].
Digre KB, Varner MW, Corbett JJ. Pseudotumor cerebri and pregnancy. Neurology. 1984 Jun. 34(6):721-9. [Medline].
Giuseffi V, Wall M, Siegel PZ, Rojas PB. Symptoms and disease associations in idiopathic intracranial hypertension (pseudotumor cerebri): a case-control study. Neurology. 1991 Feb. 41(2 ( Pt 1)):239-44. [Medline].
Hughes S. Drug Improves Vision in Idiopathic Intracranial Hypertension. Medscape Medical News. Available at http://www.medscape.com/viewarticle/824073. Accessed: April 29, 2014.
Wall M, McDermott MP, Kieburtz KD, Corbett JJ, Feldon SE, Friedman DI, 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 23-30. 311(16):1641-51. [Medline].
Goh KY, Schatz NJ, Glaser JS. Optic nerve sheath fenestration for pseudotumor cerebri. J Neuroophthalmol. 1997 Jun. 17(2):86-91. [Medline].
Brazis PW. Clinical review: the surgical treatment of idiopathic pseudotumour cerebri (idiopathic intracranial hypertension). Cephalalgia. 2008 Dec. 28(12):1361-73. [Medline].
Chandrasekaran S, McCluskey P, Minassian D, Assaad N. Visual outcomes for optic nerve sheath fenestration in pseudotumour cerebri and related conditions. Clin Experiment Ophthalmol. 2006 Sep-Oct. 34(7):661-5. [Medline].
Spoor TC, McHenry JG. Long-term effectiveness of optic nerve sheath decompression for pseudotumor cerebri. Arch Ophthalmol. 1993 May. 111(5):632-5. [Medline].
Nithyanandam S, Manayath GJ, Battu RR. Optic nerve sheath decompression for visual loss in intracranial hypertension: report from a tertiary care center in South India. Indian J Ophthalmol. 2008 Mar-Apr. 56(2):115-20. [Medline]. [Full Text].
Yadav YR, Parihar V, Agarwal M, Bhatele PR, Saxena N. Lumbar peritoneal shunt in idiopathic intracranial hypertension. Turk Neurosurg. 2012. 22(1):21-6. [Medline].
Burgett RA, Purvin VA, Kawasaki A. Lumboperitoneal shunting for pseudotumor cerebri. Neurology. 1997 Sep. 49(3):734-9. [Medline].
Woodworth GF, McGirt MJ, Elfert P, Sciubba DM, Rigamonti D. Frameless stereotactic ventricular shunt placement for idiopathic intracranial hypertension. Stereotact Funct Neurosurg. 2005. 83(1):12-6. [Medline].
Sinclair AJ, Kuruvath S, Sen D, Nightingale PG, Burdon MA, Flint G. Is cerebrospinal fluid shunting in idiopathic intracranial hypertension worthwhile? A 10-year review. Cephalalgia. 2011 Dec. 31(16):1627-33. [Medline].
Bussière M, Falero R, Nicolle D, Proulx A, Patel V, Pelz D. Unilateral transverse sinus stenting of patients with idiopathic intracranial hypertension. AJNR Am J Neuroradiol. 2010 Apr. 31(4):645-50. [Medline].
Arac A, Lee M, Steinberg GK, Marcellus M, Marks MP. Efficacy of endovascular stenting in dural venous sinus stenosis for the treatment of idiopathic intracranial hypertension. Neurosurg Focus. 2009 Nov. 27(5):E14. [Medline].
Fridley J, Foroozan R, Sherman V, Brandt ML, Yoshor D. Bariatric surgery for the treatment of idiopathic intracranial hypertension. J Neurosurg. 2011 Jan. 114(1):34-9. [Medline].
Johnson LN, Krohel GB, Madsen RW, March GA Jr. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology. 1998 Dec. 105(12):2313-7. [Medline].
Pollak L, Zohar E, Glovinsky Y, Huna-Baron R. Reevaluation of presentation and course of idiopathic intracranial hypertension - a large cohort comprehensive study. Acta Neurol Scand. 2012 Dec 31. [Medline].