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Show lou",al of Clinical Neuro-ophthalmo!ogy 8(2): 93-98, 1988. Treatment of Pseudotumor Cerebri with Diamox (Acetazolamide) Robert L. Tomsak, M,D., Ph.D., Arysol S. Niffenegger, and Bernd F. Remler, M.D. © 1988 Raven Press, Ltd., New York Four patients with idiopathic pseudotumor cerebri were treated with Diamox, 1000 mg/day orally in divided dosages. Photographically documented resolution of papilledema was noted to begin after an average treatment period of 40 days and was complete in three patients by 91 days. The efficacy of Diamox in the treatment of papilledema resulting from pseudotumor cerebri has not been previously documented by fundus photographs. Key Words: Pseudotumor cerebri-Diamox-Acetazolamide- Papilledema-Increased intracranial pressure. From the Division of Neuro-ophthalmology, Department of Neurology (RL.T., B.F.R.), and the Department of Surgery, Division of Ophthalmology (RL.T.), University Hospitals of Cleveland and Case Western Reserve University School of Medicine (RL.T., A.5.), Cleveland, Ohio. Address correspondence and reprint requests to Dr. R. L. Tomsak at Lakeside Hospital, Neurology 3200A, 2074 Abington Rd., Cleveland, OH 44106, U.S.A. 93 The most serious complication of pseudotumor cerebri is permanent visual loss from optic atrophy secondary to chronic papilledema. Although pseudotumor cerebri may resolve spontaneously (1), various degrees of visual loss in about 50% of patients stresses the need for adequate therapy (2,3). Increased intracranial pressure in pseudotumor cerebri seems to result from impaired absorbtion of cerebrospinal fluid outflow by the arachnoid granulations (4-6). Since there are no drugs available that increase cerebrospinal fluid absorbtion, the pharmacologic management of pseudotumor cerebri is aimed at inhibiting cerebrospinal fluid production. Diuretics, steroids, or both are used by some clinicians as first line therapeutic agents but the results of their use have not been entirely satisfactory (7). Surgical approaches include repeated lumbar punctures, lumbar-peritoneal shunt, and optic nerve sheath decompression and are usually recommended when medical therapy fails and when the risk of visual loss is severe (7-9). Herein we report the rapid resolution of papilledema in four patients with pseudotumor cerebri who were treated with standard doses of Diamox alone. METHODS AND RESULTS Our patients were all women; three were black and one was white. All four patients met Dandy's criteria (10,11) for the diagnosis of pseudotumor cerebri: (a) increased intracranial pressure; (b) normal neurologic examination except for transient abducens palsy (cases 2, 3, and 4); (c) normal cerebrospinal fluid composition; (d) normal or small ventricular size. Best corrected visual acuity was determined for 94 R. L. TOMSAK ET AL. TABLE 1. Summary of patients with pseudotumor cerebri treated with Diamox Age (years) Sex/race Complaints Predisposing factors CT scan Spinal fluid opening pressure (mm H20) Days until resolution of papilledema first noted Days until resolution of papilledema complete Follow-up (months) Case 1 Case 2 Case 3 Case 4 30 42 23 41 F/W FIB FIB FIB Headaches Blurred and Headaches. Headaches, double vision blurred and blurred and double vision double vision Obesity Unknown Obesity Obesity Normal Normal Normal Normal 350 550 302 340 37 46 57 20 85 87 102 NA 7.0 6.5 6.5 1.5 NA, not aplicable. distance and near and '..vas 20/25 or better upon presentation in all patients. Color vision measured by pseudoisochromatic plates, Amsler grid testing, and pupillary examinations were normal. Visual fields were done using the Goldmann pe-rimeter. Enlargement of the blind spots were noted in all patients. In addition, mild binasal inferior field constriction was present in case 4. These visual field abnormalities resolved after treatment with Diamox in all cases. ... \ .:-' "hI E:/O ann (B) left eye before Diamox therapy. (C) Right eye and (0) left eye after 37 days of I elm Ncuro-ophthalmol, Vol. 0, No.2, 1':/08 TREATMENT OF PSEUDOTUMOR CEREBRI 95 FIG. 2. Cas€ 2. (AJ Riglit eye and (a, left eye before Diamox therapy. (C) Right eye and (0) left eye after 87 days of Diamox therapy. After pharmacologic mydriasis, the optic discs were carefully examined using binocular indirect ophthalmoscopy and stereoscopic slit lamp biomicroscopy with Hruby, Yolk, or fundus contact lenses. Lastly, Kodachrome slides of the optic discs were taken as a baseline and at each followup visit. Computed tomography (CT) scans with and without contrast and single lumbar punctures were also performed. All patients were treated with Diamox, 1000 mg/day orally, in divided doses. Follow-up exams were performed in 3 to 8 week intervals. Resolution of papilledema was first noted within 20 to 57 days (mean 40 days). In cases 1 through 3, papilledema was completely resolved after 85-102 days (mean 91 days), at which point therapy was stopped. Patients have been followed for an average of 5.3 months (range 1.5 to 7 months); no recurrences have been observed as yet. Case 4 continues to undergo treatment. Table 1 summarizes the findings for all four patients; Fig. 1-16 show the appearance of the optic discs before and after Diamox therapy. DISCUSSION Diamox is a frequently used and recommended drug in the treatment of pseudotumor cerebri (12). Surprisingly, however, little proof exists of its efficacy. In a review of 51 pseudotumor cerebri cases, Lubow and Kuhr (13) reported 7 patients whose papilledema resolved after Diamox therapy. However, specific details of treatment and optic disc photographs were not provided. Miller (14) showed disc photos of a patient whose papilledema began to resolve after 1 month of treatment with "dehydrating agents," but the specific compound was not identified. Our four patients responded rapidly after initiation of therapy with Diamox. It could be argued that the papilledema resolved as part of the natural history of their disease. This is, however, an unlikely explanation since the mean duration of pseudotumor cerebri is about 8 months and sometimes longer (9). In addition, fully developed papilledema usually requires 6 to 8 weeks to resolve after neurosurgical decompression of the cerebro- I Cli" NeIlYO-0I'"I"a/mo/, Vol. 8, No.2, 1988 96 R. L. TOMSAK ET AL. • FIG. 3. Case 3. (A) Right eye and (B) left eye before Diamox therapy. (C) Right eye and (D) left eye 57 days after Diamox therapy. spinal fluid compartment (14). Thus, resolution of papilledema in our cases is most likely the result of the salutary effect of Diamox. Multiple studies have demonstrated that acetazolamide is effective in decreasing cerebrospinal fluid pressure in animals and humans (15-20). Diamox decreases cerebrospinal fluid production by inhibition of carbonic anhydrase, resulting in decreased sodium ion transport across the choroidal epithelium (17-19). Carbonic anhydrase indirectly supplies the cell with hydrogen and bicarbonate ions by catalyzing the formation of carbonic acid from H20 and CO2 , Once inside the cell, carbonic acid readily dissociates into a hydrogen and a bicarbonate ion. These ions can then be exchanged for sodium via the Na + ,K + -ATPase pump. The transport of Na establishes an osmotic gradient that facilitates water diffusion and thereby the production of cerebrospinal fluid. Tschirgi and associates (16) found in cats that administration of 150 mg/kg of soluble acetazolamide decreased the rate of cerebrospinal fluid production by 66% and the intracranial pressure :"'"""CJ'''' clnd Luck (19) found that the rate I Clill Nt'urv-ophthalmvl, Vlli. ~', Nt•. 2, 1'9,),) of sodium transport in rabbit cerebrospinal fluid decreased by 40% after Diamox treatment while the flux of other solutes was unaffected. According to Vogh and Doyle (20), the maximum effective dose of Diamox in decreasing cerebrospinal fluid production in rats is 20 mg/kg. This dose translates to 1400 mg for a 70 kg human. They also found that other carbonic anhydrase inhibitors, including Neptazane (methazolamide), were less effective in reducing the entry of sodium ions into rat cerebrospinal fluid (20). Whether Neptazane is less effective than Diamox in the treatment of pseudotumor cerebri is unknown. The use of Diamox is sometimes limited by its well known side effects: paresthesias, drowsiness, nausea, general malaise, metabolic acidosis, altered taste, and renal calculi (21). Three of our patients complained of paresthesias and one also complained of a dry mouth and sore tongue. These minor side effects did not interfere with treatment and were a useful indication of therapeutic compliance. Use of the long acting form of the drug (Diamox Sequels) seems to be associated with less side effects (21). TREATMENT OF PSEUDOTUMOR CEREBRI 97 FIG. 4. Case 4. (A) Right eye and (8) left eye before Diamox therapy. (C) Right eye 20 days after Diamox therapy. Note resolution of disc hemorrhages seen in (A). (0) Left eye after 20 days of Diamox therapy. Note beginning of resolution of optic disc edema. In summary, three patients suffering from pseudotumor cerebri were completely free of signs and symptoms after 3 months of treatment with 1000 mg of Diamox each day. The fourth patient's papilledema began to resolve after 3 weeks of treatment and is presently being continued. Acetazolamide is a logical first drug of choice for reducing intracranial pressure and preventing visual field loss in patients with idiopathic pseudotumor cerebri. We do not know if our patients represent a subset of pseudotumor cerebri sufferers who are rapid responders to Diamox; a larger longitudinal study would be needed to prove or disprove this speculation. We recommend close and careful follow-up of patients in the active stages of pseudotumor cerebri and encourage the use of serial optic disc photographs to aid in monitoring the course of the disease and response to therapy. REFERENCES 1. Rabinowicz 1M, Ben-Sira I. Zauberman H. Preservation of visual function in papilloedema observed 3 to 6 years in cases of benign intracranial hypertension. Br I Ophtlzalmol 1968;52:236-41. 2. Corbett JJ, Savino PI. Thompson HS, et al. Visual loss in pseudotumor cerbri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neural 1982;39:461-74. 3. Troost BT, Sufit RL, Grand MG. Sudden monocular visual loss in pseudotumor cerebri. Arch Neurol 1979;36:440-2. 4. Fishman RA. Cerebrospillal fillid ill diseases of the lleTl'OllS system. Philadelphia: W.B. Saunders, 1980. . 5. Davson H. The little brain. The Bowman Lecture, 1979. TrailS Ophthalmol Soc UK 1979;99:21-37. 6. Upton ML, Weller RO. The morphology of cerebrospinal fluid drainage pathways in human arachnoid granulations. I NellroslIrg 1985;63:867-75. 7. Corbett JJ. Problems in the diagnosis and treatment of pseudotumor cerebri. Call I Nellrol Sci 1983;10:221-9. 8. Hupp SL, Glaser jS, Frazier-Byrne S. Optic nerve sheath decompression. Review of 17 cases. Arch Ophthalmol 1987;105:386-9. 9. Tomsak RL, Sweeney Pj. Pseudotumor cerebri: some neuro-ophthalmologic perspectives. In: Daroff RB, Conomy jP, eds. COlltril1lltiolls to call temporary Ileurology: a tribllte to {oseph M. Foley. Stoneham, MA. Butterworth, 1988. 10. Dandy WE. Intracranial pressure without brain tumor: diagnosis and treatment. Alln SlIrg 1937;106:492-513. 11. Smith jL. Pseudotumor cerebri. Trans Am Acad Ophthalmol Otolaryngol 1958;62:432-40. 'Clill Neuro-aphtha/mol, Vol. 8, No.2. 1988 98 R. I. TOMSAK ET AI. 12. Burde RM, Savino PI, Trobe JD. Clinical decisions in neuroophthalmology. St. Louis: C. V. Mosby, 1985:124-6. 13. Lubow M, Kuhr L. Pseudotumor cerebri: comments on practical management. In: Glaser JS, Smith JL, eds. Neuroophthalmology, Vol. IX. St. Louis: C. V. Mosby, 1976:199206. 14. Miller NR. Walsh and Hoyfs clinical neuro-ophthalmology, 4th ed., Vol 1. Baltlmore: Williams and Wilkins, 1982:186-7. 15. Maren TH, Robinson B. The pharmacology of acetazolamIde as related to cerebrospinal fluid and the treatment of hydrocephalus. john Hopkins Hosp Bull 1960;106:1-24. 16. Tschirgi RD, Frost RW, Taylor JL. Inhibition of cerebrospinal fluid formation by a carbonic anhydrase inhibitor, 2-acetyl-l,3,4-thiadiazole-5-sulfonamide (Diamox). Proc Soc Exp Bioi Med 1954;87:373-6. I Cli1l NC1IYO-ophthl1lmoJ. Vol. s. ;'\:\.. ) 17. Maren TH. Carbonic anhydrase: chemistry, physiology and inhibition. Phl{siol Rev 1967;47:595-781. 18. Davson H, Segal MB. The effects of some inhibitors and accelerators of sodium transport on the turnover of 22Na in the cerebrospinal fluid and the brain. j Physiol (Lond) 1970;209:131-53. 19. Davson H, Luck CPo The effect of acetazolamide on the chemical composition of the aqueous humor and cerebrospinal fluid of some mammalian species and on the rate of turnover of 24Na in these fluids. j Physiol (Lond) 1957;137: 279-93. 20. Vogh BP, Doyle AS. The effect of carbonic anhydrase inhibitors and other drugs on sodium entry to cerebrospinal fluid. j Pharmacol Exp Ther 1981;217:51-6. 21. Lichter PR. Reducing side effects of carbonic anhydrase inhibitors. Ophthalmology 1981;88:266-9. |
