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Pseudotumor Cerebri Secondary to MinocyclineIntake Earl Robert G. Ang, MD, J. C. Chava Zimmerman, MD, and Elissa Malkin, DO, MPH Background: Pseudotumor cerebri, or idiopathic intracranial hypertension, is a condition most com-
monly affecting women of childbearing age who are obese or who have experienced recent weight gain.
Frequently the patient complains of headache accompanied by dizziness, nausea, or visual defects, and it is
characterized by elevated intracranial pressure in the absence of a space-occupying lesion or infection
Methods: A patient had been prescribed minocycline and subsequently developed symptoms 6 weeks
after an increase in the original dosage. She was initially examined by an ophthalmologist, then was
sent to the Emergency Department, and finally admitted under the family practice service. Articles were
searched through MEDLINE, MD Consult, and Google. Key words included “pseudotumor cerebri,” be-
nign intracranial hypertension,” idiopathic intracranial hypertension,” and “minocycline.”
Results and Conclusion: Although the pathogenesis of pseudotumor cerebri is not completely un-
derstood, an association has been observed with minocycline use. This report describes a 16-year-old
girl who developed idiopathic intracranial hypertension while taking minocycline for acne. Symptoms of
blurred vision and severe headache unrelated to position or activity; an absence of fever, bilateral disk
edema, and focalizing neurologic signs; negative neuroradiographic findings; increased cerebrospinal
fluid pressure with a normal cell count; and exclusion of systemic or structural cause of increased intra-
cranial pressure satisfy the criteria for the diagnosis of idiopathic intracranial hypertension. Minocy-
cline is often used by family physicians for the treatment of acne, and this complication requires vigi-
lance to protect against potential vision loss. (J Am Board Fam Pract 2002;15:229 –33.)
Idiopathic intracranial hypertension is a distinct sulting ophthalmologist, and the recommendations syndrome in which patients have intracranial hy- of the consulting neurologist were reviewed. A pertension, papilledema, an absence of focal neu- MEDLINE and MD Consult literature review was rologic signs, and essentially normal cerebrospinal undertaken using the key words “pseudotumor fluid. Benign intracranial hypertension, as it is also cerebri,” “benign intracranial hypertension,” idio- known, is usually a self-limited condition, although pathic intracranial hypertension,” and “minocy- in some instances it can be a chronic condition.
Annual incidence varies from 1 to 2 cases per100,000 persons; however, among obese women inthe reproductive age-group, the incidence jumps to Case Report
19 to 21 cases per 100,000.1 The pathogenesis and A 16-year-old girl complained of a 3-day history of severe headache, described as dull, nonradiating,and continuous, associated with blurred vision localized to the occipital region. There was no A case is reported of a patient admitted through the relation between the symptoms and position or Emergency Department after being seen by an activity. She had no history of fever, nausea, or ophthalmologist for headaches and blurred vision.
vomiting, nor was there a history of trauma. Acet- Information regarding her case was obtained by aminophen and ibuprofen brought little relief of chart reviews, interviews with the patient and her the symptoms. With the persistence of the symp- family, the attending family physician, and the con- toms, as well as development of a slightly stiff neck,the patient was brought to an ophthalmologist. Onexamination, she was found to have bilateral disk Submitted, revised, 19 September 2001.
From the St. Francis Hospital of Evanston Family Prac- edema consistent with increased intracranial pres- tice Residency Program (ERGA, JCCZ, EM), Evanston, Ill.
sure and was subsequently sent to the emergency Address reprint requests to Earl Robert G. Ang, MD, 5510Lincoln Ave, Unit 104, Morton Grove, IL 60053-3480.
department for further evaluation and treatment.
The patient’s medical, surgical, and family his- admitted to the hospital under the care of the tory were all unremarkable. She did not smoke and family physician who originally prescribed the mi- denied alcohol and illicit drug use. She had been nocycline. Acetazolamide, 500 mg twice daily, was taking minocycline, 50mg orally twice daily, for her continued, and minocycline was discontinued. A acne as prescribed by her family physician for more neurological consultant suggested magnetic reso- than a year. Recently, under the guidance of her nance imaging (MRI) and magnetic resonance an- physician, she doubled the dose to 100 mg orally giography (MRA) to exclude the possibility of a twice daily 6 weeks before the onset of her symptoms.
sinovenous thrombosis. Findings of both MRI and When examined, she was a well-developed girl MRA were normal. The patient’s headache began of normal weight, who was alert, oriented, and in to improve, but it was now dependent more on no acute distress. Her temperature was 97.6°F, position. The blurred vision persisted, however.
pulse was 67 beats per minute, respirations were The patient was released from the hospital the next 16/min, and blood pressure was 149/82 mm Hg.
day with a prescription for acetazolamide.
Her face had scattered erythematous papules and One week after discharge, when the patient was pustules, especially on the cheeks and forehead.
seen for a follow-up examination in the outpatient Her pupils were bilaterally dilated as a result of the clinic, she stated that the headaches, which re- topical cycloplegic medication given earlier. Mild mained postural, had improved. She still had pap- papilledema was seen bilaterally on funduscopic illedema. She had stopped taking the acetazolamide examination. Extraocular movements were intact, because of nausea, so caffeine was recommended and there was no ptosis or nystagmus. Her uncor- for her postural headaches. The patient and her rected visual acuity was 20/25 in the right eye, and parents were told to telephone if her symptoms got 20/100 in the left eye. No gross deficit in the visual worse or failed to resolve, and she was advised to fields was observed using confrontation testing.
continue follow-up visits with the ophthalmologist to The patient did not wear eyeglasses or contacts.
ensure there was no deterioration of her visual acuity.
Both of her tympanic membranes were intact, andthere was no evidence of bulging or discharge. Herneck was supple and was negative for Kernig and Discussion
Brudzinski signs. There was no lymphadenopathy.
The syndrome of intracranial hypertension with There was some neck pain when the patient flexed papilledema, no focal neurologic deficit, normal her neck, but motion was not limited. Findings of cerebrospinal fluid, and normal to small ventricles an examination of the lungs, heart, and abdomen was described nearly a century ago by Quinke2 as were benign. Neurologically her cranial nerves II serous meningitis. Other names include otitis hy- to XII were intact, manual muscle testing in all drocephalus, toxic hydrocephalus, sinus thrombosis extremities was 5/5, and deep-tendon reflexes were causing intracranial hypertension, hypertensive all 2/4. Cerebellar function was intact, as was gait, meningeal hydrops, pseudoabscess, intracranial and Babinski reflexes were downward bilaterally.
pressure without brain tumor, brain swelling of Sensation was intact to pain and soft touch.
unknown cause, and pseudotumor cerebri.
A complete blood count and basic metabolic Modified Dandy criteria1 for the diagnosis of panel returned the following values: white cell idiopathic intracranial hypertension include signs count 7.23 ϫ 103/␮L, hemoglobin 15.0g/dL, he- and symptoms of increased intracranial hyperten- matocrit 43.8%, and platelet count 226 ϫ 103/␮L, sion2 and no localizing neurologic signs (other than and her sodium, potassium, magnesium, and chlo- abducens nerve paralysis3) in an awake and alert ride levels were all within normal limits. A com- patient, normal imaging studies except for small puterized tomographic (CT) scan of the brain ventricles or empty sella,4 increased lumbar pres- showed normal findings. Lumbar puncture was sure (Ն25 cm of water) with normal cerebral spinal performed, and the opening pressure was 55 cm fluid,5 and no primary structural or systemic causes H2O. Findings from cerebral spinal fluid analysis were essentially normal, and a diagnosis of pseudo- In a retrospective review of 120patients by Weisberg,4 99% of patients had headaches, and The patient was given 500 mg of oral acetazol- 35% had visual changes. In a study of cases of amide in the emergency department, and she was idiopathic intracranial hypertension in an emer- 230 JABFP May–June 2002 Vol. 15 No. 3
gency department, Jones et al5 found that the mean nal insufficiency, Cushing disease, hypoparathy- patient age was 27 Ϯ 8.9 years, 83% were women, roidism, hypothyroidism, chronic renal failure, and and 67% were obese. Ninety-two percent com- plained of headache, 75% had nausea and vomiting, Of particular interest, especially in this case, is 71% reported dizziness, and 65% had disturbances the association of intracranial hypertension with of visual acuity. Other symptoms included photo- medication intake. Minocycline-related pseudotu- sensitivity, diplopia, stiff neck, paresthesias, myal- mor cerebri was first reported in 1978,7 Since then gias, tinnitus, and vertigo. Bilateral papilledema 16 additional cases have been reported. Chiu et al,8 was observed in 67%, 54% had a visual field defect, in a retrospective study, reviewed 12 cases of mi- and 29% had sixth cranial nerve palsy. Four percent nocycline-induced pseudotumor cerebri syndrome.
had seventh cranial nerve palsy. If ocular motility Seventy-five percent of the patients developed defects other than from the sixth cranial nerve are pseudotumor cerebri within 8 weeks of starting encountered, the diagnosis of idiopathic intracra- minocycline. Six (50%) of the patients were not nial hypertension is less likely. Unilateral papill- obese. Two patients developed symptoms after 1 edema is also possible, although less common, and year of minocycline use. Pseudotumor cerebri was is not associated with the duration of disease or diagnosed by finding papilledema on routine exam- severity of symptoms. It should also be noted that ination in 1 patient who was asymptomatic after idiopathic intracranial hypertension can occur in taking minocycline for 1 year. After discontinuing the absence of headache or papilledema.
minocycline, all patients recovered from pseudotu- CT and MRI findings are typically normal, al- mor cerebri syndrome, and after at least 1 year of though there might be nonspecific findings, such as follow-up, there were no recurrences.
empty sella, prominent cisterna magna, and dilated Four cases of minocycline-induced intracranial optic nerve sheaths. In a study of 29 male patients hypertension were documented in Australia by with idiopathic intracranial hypertension by Digre Lander.9 Durations of therapy ranged from 25 days and Corbett,6 an empty sella was noted in 55% of to 18 months. All had severe headaches and papill- edema, and visual disturbance was reported in two Cerebrospinal fluid pressure should be elevated, cases. Cessation of minocycline reversed the intra- and the protein levels should be low or normal, cranial hypertension, although 1 patient had per- glucose levels normal, and cell counts normal. A sistent lower nasal quadrantic field-of-vision loss 6 diagnosis of idiopathic intracranial hypertension months later. In all cases, the diagnosis was missed should not be made without performing a lumbarpuncture. An opening pressure of greater than 250 by the primary care physician. The ability of minocycline to decrease cerebrospinal fluid absorp- 2O is diagnostic. When clinical and radiologic evidence is highly indicative of idiopathic intracra- tion is the postulated mechanism for minocycline- nial hypertension, and the opening pressure is nor- induced pseudotumor cerebri. Isotretinoin, tetra- mal, a second lumbar puncture or continuous in- cycline, trimethoprim-sulfamethoxazole, cimetidine, tracranial pressure monitoring might be necessary.
corticosteroids, tamoxifen, lithium, nitrofurantoin, Intracranial sinus thrombosis, which is associ- and levothyroxine have been implicated in addition ated with head injury, otitis media, and hypercoag- ulable and hyperviscosity syndromes, most often The only serious complication of idiopathic in- causes intracranial hypertension without focal neu- tracranial hypertension is vision loss, which can be rologic defect. Findings of a CT scan and cerebro- sudden or gradual and can occur at any time during spinal fluid are normal, although an MRI might the course of the disease. Appropriate treatment show an abnormality, especially in the transverse can prevent vision loss, however. Risk factors for sinus. MRA and digital subtraction confirm the vision loss include duration of related symptoms before diagnosis, systemic hypertension, anemia, Epidemiologic studies have confirmed an asso- older age, and high degrees of myopia. African ciation between female sex, reproductive age- American men also appear to be at higher risk.
group, menstrual irregularity, obesity, and recent Studies have shown that perimetry, using either the weight gain. Other associated conditions, although Goldman manual perimeter or a computed auto- unconfirmed by case-control studies, include adre- mated perimeter, is the best test to detect and monitor vision loss associated with idiopathic in- creased opening pressure on a lumbar puncture with a normal cerebrospinal fluid findings, and no Treatment is directed at preventing vision loss structural or systemic cause for intracranial hyper- and treating the cephalgia. Initially, predisposing tension. It is most often seen in reproductive-age factors should be corrected, such as stopping pos- women who are obese, who have recently gained sible inciting medications and or treating any un- weight, and who have irregular menses. Although derlying medical condition. Lumbar puncture, an abducens nerve palsy might be observed, any aside from being diagnostic, is therapeutic. If the other ocular motility disorder makes the diagnosis symptoms resolve after the initial lumbar puncture, of idiopathic intracranial hypertension unlikely. Id- no further action is warranted. If the symptoms are iopathic intracranial hypertension can be associated unresolved, repeated lumbar punctures, up to four with endocrine dysfunction, systemic lupus ery- in the first 2 to 4 weeks, are recommended. Beyond thematosus, chronic renal failure, and with some the first 4 weeks, repeated lumbar punctures are A history of minocycline use should be deter- Acetazolamide (Diamox), a carbonic-anhydrase mined in cases of pseudotumor cerebri, especially inhibitor, is frequently used for idiopathic intracra- when the patient is not obese. Minocycline is nial hypertension. Treatment is started at a dosage among the top four oral antibiotics most commonly of 250mg/d and gradually increased until target prescribed for the treatment of acne, with more doses of 500 mg four times a day is reached or until than 374,000 prescriptions written a year.11 Family side effects are encountered. Adverse reactions in- physicians who prescribe minocycline should be clude paresthesias, drowsiness, nausea, malaise, vigilant, as this potential complication is not en- metabolic acidosis, altered taste, and renal calculi.
tirely benign. Patients must be aware of the symp- For those who are intolerant or unresponsive to toms and seek medical attention should they arise.
acetazolamide, a short course of oral corticoste- Additionally, physicians should be knowledgeable roids might be of benefit. Prednisone, 40to 60 of this complication, screen their patients with mg/d, should resolve symptoms in 10to 14 days, at questions regarding the symptoms of intracranial which point the medication is tapered for the next hypertension, and routinely perform ophthalmo- logic examinations of their patients who are taking Surgery should be considered when vision loss this medication. Treatment, which is directed to- does not respond to medical treatment, when initial ward the prevention of visual loss by correcting vision loss is severe, or when the patient response is predisposing factors, includes lumbar puncture, se- unreliable at visual field testing and there is an rial if necessary, acetazolamide, corticosteroids if increased delay in the major positive peak of visual there is no response to acetazolamide, or surgery evoked response. Surgical options include lumbo- when visual loss is severe or unresponsive to med- peritoneal shunt or optic nerve decompression.
Fenestration of the optic nerve sheaths is becomingthe treatment of choice. It provides immediate de-compression of the optic nerve, as well as long- References
term filtration of cerebrospinal fluid. Complica- 1. Duncan FJ, Corbett JJ, Wall M. The incidence of tions include papillary dysfunction, peripapillary pseudotumor cerebri. Population studies in Iowa andLouisiana. Arch Neurol 1988;45:875–7.
hemorrhage, chemosis, and chorioretinal scarring.
Although lumboperitoneal shunting has been 2. Quinke H. Ueber Meningitis serosa und verwandte Zustande. Dtsch Z Nervenheilk 1897;9:149 – 68.
shown to fail to prevent the progression of visionloss,10 this procedure is appropriate in those who 3. Radhakrishnan K, Ahlskog JE, Garrity JA, Kurland LT. Idiopathic intracranial hypertension. Mayo Clin do not respond to optic nerve fenestration.
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6. Digre KB, Corbett JJ. Pseudotumor cerebri in men.
9. Lander CM. Minocycline-induced benign intracra- nial hypertension. Clin Exp Neurol 1989;26:161–7.
7. Monaco F, Agnetti V, Mutani R. Benign intracranial 10. Rosenberg M, Smith C, Beck R, Corbett J, et al. The hypertension after minocycline therapy. Eur Neurol efficacy of shunting procedures in pseudotumor cerebri. Neurology 1989;39(Suppl 1):209.
8. Chiu A, Chuenkongkaew WL, Cornblath WT, et al.
11. Stern RS. Medication and medical service utilization Minocycline treatment and pseudotumor cerebri for acne 1995–1998. J Am Acad Dermatol 2000;43: syndrome. Am J Ophthalmol 1998;126:116 –21.

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