Pseudohypoparathyroidism

Benign intracranial hypertension is a cause of progressive visual loss in children and young adults. Diagnosis is primarily clinical and requires radiographic exclusion of an intracranial mass and measurement of cerebrospinal fluid pressure. Treatment is directed at reducing intracranial pressure in idiopathic cases or correcting associated conditions. Carbonic anhydrase inhibitors, loop diuretics and steroids have been used for treatment. Adjunctive surgery may be indicated in cases of rapid vision loss or if medical treatment fails. Benign intracranial hypertension tends to be self-limited, with a course of less than 12 months in most cases.

Benign intracranial hypertension (also called pseudotumor cerebri) is an uncommon cause of visual loss. Patients may consult a family physician when symptoms first arise, and familiarity with this condition and its initial treatment can lead to early diagnosis and appropriate therapy. The visual loss may be reversed if treatment is instituted promptly.

Epidemiology

The prevalence of benign intracranial hypertension has been estimated to range from 1 to 19 cases per 100,000 population.[1] Women are affected eight times more frequently than men.[2] A typical patient is an obese female of childbearing age; however, the condition can develop at any age. Recent studies indicate that benign intracranial hypertension is more prevalent in children than was previously thought.[3]

Etiology

Benign intracranial hypertension was first described by Quincke in 1896, but the cause of this disorder continues to be a source of speculation. The pathophysiologic basis of benign intracranial hypertension remains unclear but is associated with the conditions listed in Table 1.[3-5] These conditions can be categorized as aberrations in intracranial volume regulation, metabolic diseases, medication-associated abnormalities and miscellaneous disorders. TABLE 1 Conditions Seen in Conjunction with Benign Intracranial Hypertension Cerebrovascular Increased intracranial blood volume Increased venous pressure Right heart failure Superior vena cava syndrome Venous sinus thrombosis Cerebral edema

Interstitial

Vasogenic

Cytotoxic Cerebrospinal fluid-related Overproduction of fluid Underabsorption of fluid Increased arachnoidal resistance Metabolic Obesity Thyroid disease Addison's disease Pregnancy Hypoparathyroidism Pseudohypoparathyroidism Menstrual cycle abnormalities Vitamin D-deficient rickets Pharmacologic Steroids (therapy and withdrawal) Estrogens Thyroid supplements Tetracycline Nalidixic acid (NegGram) Vitamin A Lithium Miscellaneous Systemic lupus erythematosus Polyarteritis nodosa Guillain-Barre syndrome Iron deficiency anemia Metastatic thyroid anemia Adapted from Baker, et al.,[3] Lehman[4] and Susman.[5]

Clinical Aspects

HISTORY

Diagnosis of benign intracranial hypertension is based on a careful history. Several large series indicate that headache is the most common presenting symptom. The headache is most frequently described as throbbing, episodic and without localization. It is exacerbated by the Valsalva maneuver and head movement and is most severe in the morning. Nausea is frequently associated with the headache; vomiting and dizziness are less common.

Visual changes are a frequent clue to the diagnosis. Up to 35 percent of patients report visual changes, usually preceding the headache. The most frequently reported visual changes are episodic horizontal diplopia or tangential visual obscuration.[4,6-8] Deterioration of visual acuity and scotomata have also been reported as presenting symptoms in the absence of headache.

In addition to headache, patients may report pulsatile tinnitus and pain in the shoulders, neck, back and arms.[9] The presence of these otherwise nonspecific symptoms in a person with headache and/or visual symptoms should prompt evaluation for benign intracranial hypertension.

In children, dizziness may be replaced by intermittent gait ataxia. Children may display irritable behavior rather than complain of headache.

PHYSICAL EXAMINATION

A careful, thorough physical examination will corroborate the diagnosis of benign intracranial hypertension.

Papilledema is the most frequent physical finding; its absence, however, does not exclude the diagnosis of benign intracranial hypertension. Papilledema is most often bilateral but has been reported to be unilateral, or even absent.[10] Papilledema must be differentiated from pseudopapilledema, which is a nonspecific finding. In both papilledema and pseudopapilledema, the optic disk is compact, with blurring of the disk margins. However, in pseudopapilledema the retinal vessels appear normal, the disk is not congested and there are no hemorrhages or other retinal abnormalities.

Papilledema is frequently not found in children with benign intracranial hypertension. In one series, 12 of 38 children did not have papilledema[11]; in another study, 12 of 23 children did not have papilledema.[12] Unreported in the studies, however, was the percentage of children who were infants with unfused sutures.

An enlarged blind spot and inferior nasal visual field deficits on visual field testing are the earliest, most common ocular changes in benign intracranial hypertension.[7,8,13] In up to 25 percent of patients, sixth nerve palsy is present.[6-9,13,14]

LABORATORY STUDIES

The diagnosis of benign intracranial hypertension is in large part clinical, but radiologic and laboratory studies have a role in confirming the diagnosis; lumbar puncture is the most common corroborating procedure. Neck pain should not deter lumbar puncture in the presence of normal findings on magnetic resonance imaging (MRI) or computed tomography (CT).[4] When signs of brainstem dysfunction are present, a thorough evaluation of the posterior fossa with radiologic studies and neurosurgical consultation is recommended before lumbar puncture is performed.[4] Ventricular size on MRI or CT scan is an unreliable indicator of increased intracranial pressure. Ventricles are reported as small on imaging studies in only 5 percent of cases.

The lumbar puncture shows marked elevation of opening pressure. The average opening pressure in benign intracranial hypertension is 300 mm [H.sub.2] O, but it can be as high as 600 mm [H.sub.2] O. Analysis of the cerebrospinal fluid (CSF) reveals normal cell count, glucose and sterile culture in the absence of other disease. CSF protein is usually low and not diagnostically helpful.

Extensive endocrinologic and laboratory evaluations are rarely productive. The diagnosis is made by the combination of a characteristic clinical picture, a negative radiologic evaluation and suggestive CSF manometric studies.

DIFFERENTIAL DIAGNOSIS

Benign intracranial hypertension should be differentiated from other conditions associated with headache and papilledema or visual changes. Conditions to be excluded are listed in Table 2. The importance of an accurate, timely diagnosis is obvious since the conditions in Table 2 represent potential neurologic catastrophes (with the exception of pseudopapilledema). TABLE 2 Differential Diagnosis of Benign Intracranial Hypertension Tumor, primary or metastatic

Brain

Spinal cord Arteriovenous malformation Encephalitis Sarcoidosis Hypertensive crisis Pseudopapilledema

Treatment

The main goal of treatment in benign intracranial hypertension is preservation of visual function.

MEDICAL

When benign intracranial hypertension is associated with obesity, medications, hypertension or an endocrine disorder, correction of the underlying condition may correct the benign intracranial hypertension.[15] Most patients, however, require additional treatment aimed at lowering intracranial pressure. The medical treatment of benign intracranial hypertension is summarized in Table 3. [Tabular Data 3 Omitted]

Repeated lumbar puncture has been recommended as a treatment for benign intracranial hypertension,[16] although no clear evidence of the effectiveness of this procedure as a sole treatment has been documented.[17] Removing approximately 30 mL of fluid or sufficient fluid to lower the closing pressure to 50 percent of the opening pressure is regarded as optimal. It should be remembered that CSF is produced at a rate of 0.35 mL per minute; thus CSF pressure often returns to normal within one to two hours of lumbar puncture.[18]

Despite the putative role of steroids in the genesis of benign intracranial hypertension, it has been postulated that dexamethasone (Decadron, Dexameth, etc.) decreases vasogenic edema, and this agent has been recommended for short-term (less than four weeks) treatment of benign intracranial hypertension. Doses vary from 2 mg four times daily for children[19] to 5 mg four times daily for adults.[20] At these doses, a decrease in papilledema can be expected in two weeks. After a response is noted, the medication should be tapered, usually over two weeks.

Patients who relapse during dexamethasone tapering should be treated with prednisone, 1 mg per kg per day for children and 40 to 60 mg per day in divided doses for adults.[4] As response is seen, the regimen can be converted to every-other-day dosing, then tapered as in any other condition requiring intermittent steroid use. Because of the associated development of glucose intolerance and the likelihood of steroid-related exacerbation of benign intracranial hypertension, close monitoring and prompt tapering are essential.

Patients who fail to respond to steroids require alternative therapy. Carbonic anhydrase inhibitors such as acetazolamide (Dazamide, Diamox, etc.) may be given in doses of 60 mg per kg per day for children or 500 mg two times daily for adults.[21] Patients should be advised to watch for gastrointestinal upset, loss of appetite and perioral or digital tingling while receiving this medication. Renal calculi formation and electrolyte imbalances are other potential side effects. Methazolamide (Neptazane), another carbonic anhydrase inhibitor, has better penetration of the blood-brain barrier and can be used in lower doses than acetazolamide. It does, however, have a higher incidence of drowsiness than acetazolamide.[22]

Loop diuretics such as furosemide (Lasix), in doses of 2 mg per kg three times daily for children[23] or 40 to 160 mg daily for adults,[24] may also be used. Diuretics are a helpful adjunct to carbonic anhydrase inhibitors, because they decrease total body water. There is, however, little evidence for the efficacy of diuretics.[4]

SURGICAL

Surgical intervention is indicated when there is recent visual field loss, progressive visual field loss or reduction of visual acuity not due to macular edema despite medical therapy.[17] Medical indications for surgery include severe headache recalcitrant to standard medication or lumbar puncture. Surgery is also recommended when the patient will be having treatment likely to cause hypotension, such as hemodialysis or the initiation of treatment for hypertension. Hypotension can cause sight-threatening ischemic damage to the swollen optic disk. Further indications for surgery include a high likelihood of poor patient compliance with medical therapy or inability to perform visual field testing.

Subtemporal decompression, formerly a popular treatment, is no longer performed because of the unacceptably high incidence of failure and complications such as seizure and stroke.[25] Two procedures now used for reducing intracranial pressure are lumboperitoneal shunt placement and optic nerve sheath fenestration.

A lumboperitoneal shunt (Figure 1) continuously drains excess CSF, thus functioning in a manner similar to repeated lumbar puncture. Signs and symptoms improve in most cases within one month of surgery.[26] There is, however, a high rate of shunt revision, often 50 percent,[26,27] as well as the possibility of infection.

In optic nerve sheath fenestration, a series of windows is opened in the optic nerve sheath just behind the globe (Figure 2). This decreases papilledema and improves postoperative visual acuity or visual fields in 85 to 100 percent of patients.[28,29] In one series of 57 patients,[14] 33 had unilateral fenestration of the optic nerve sheath. Of these 33 patients, 24 had bilateral reduction in papilledema. Two-thirds of the patients experienced relief of headache following the orbital procedure.

Follow-up

Family physicians who have a quantitative perimeter in the office can perform quantitative evaluations of visual fields. Assessment should be conducted on a monthly basis for six to 12 months to screen for improvement or deterioration of field loss. During these visits (or other visits), the importance of weight reduction and reporting of new symptoms can be stressed to the patient.[17] Interval examination in the family physician's office should include measurement of visual fields, tonometry and assessment of visual acuity.

If field perimetry cannot be performed in the family physician's office, ophthalmologic consultation should be obtained. An ophthalmologist can also take stereo photographs of the optic disks to detect any change in appearance and perform contrast sensitivity check-ups.[30] Follow-up, wherever performed, should include monitoring of any underlying condition as well as the benign intracranial hypertension itself.

Prognosis

Visual loss is the only known long-term sequela of benign intracranial hypertension. It occurs in 2 to 12 percent of patients.[4,31] Careful, prolonged follow-up is indicated since visual loss has been reported even years after the initial presentation of benign intracranial hypertension.[7,8] Although in most patients symptoms and signs resolve within 12 months, recurrence has been reported in 10 percent of patients, and a protracted course is seen in up to 25 percent of patients.[32] Children are not protected from the visual loss seen in adults[11,31] and also merit close follow-up. Quantitative perimetry can be performed accurately in most children and provides an excellent method of following the regression of optic changes.

Final Comment

Aside from those patients presenting with headache, most patients with benign intracranial hypertension have relatively minor symptoms. The possibility of visual loss makes the timely diagnosis and initiation of treatment for benign intracranial hypertension of paramount importance. The family physician can help the patient understand the management of this condition, including weight loss and treatment of underlying disorders, as well as the importance of close follow-up.

REFERENCES

[1]Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol 1988;45:875-7. [2]Digre KB, Corbett JJ. Pseudotumor cerebri in men. Arch Neurol 1988;45:866-72 [Published erratum appears in Arch Neurol 1989;46:172]. [3]Baker RS, Baumann RJ, Buncic JR. Idiopathic intracranial hypertension (pseudotumor cerebri) in pediatric patients. Pediatr Neurol 1989;5:5-11. [4]Lehman LB. Pseudotumor cerebri: an enigmatic process. Hosp Prac [Off] 1988;23:127-8,130. [5]Susman JL. Benign intracranial hypertension. J Fam Pract 1990;30:290-2. [6]Rush JA. Pseudotumor cerebri: clinical profile and visual outcome in 63 patients. Mayo Clin Proc 1980;55:541-6. [7]Corbett JJ, Savino PJ, Thompson HS, 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;39:461-74. [8]Sedwick LA, Burde RM. Unilateral and asymmetric optic disk swelling with intracranial abnormalities. Am J Ophthalmol 1983;96:484-7. [9]Spence JD, Amacher AL, Willis NR. Benign intracranial hypertension without papilledema: role of 24-hour cerebrospinal fluid pressure monitoring in diagnosis and management. Neurosurgery 1980;7:326-36. [10]Couch R, Camfield PR, Tibbles JA. The changing picture of pseudotumor cerebri in children. Can J Neurol Sci 1985;12:48-50. [11]Amacher AL, Spence JD. Spectrum of benign intracranial hypertension in children and adolescents. Childs Nerv Syst 1985;1:81-6. [12]Lessell IM, Wanger SL. Pseudotumor cerebri. A not-always-benign imposter. Postgrad Med 1984;75:59-66. [13]Round R, Keane JR. The minor symptoms of increased intracranial pressure: 101 patients with benign intracranial hypertension. Neurology 1988;38:1461-4. [14]Corbett JJ, Thompson HS. The rational management of idiopathic intracranial hypertension. Arch Neurol 1989;46:1049-51. [15]Weisberg LA. Benign intracranial hypertension. Medicine 1975;54:197-207. [16]Cutler RW, Page L, Galicich J, Watters GV. Formation and absorption of cerebrospinal fluid in man. Brain 1968;91:707-20. [17]Wall M. Contrast sensitivity testing in pseudotumor cerebri. Ophthalmology 1986;93:4-7. [18]Weisberg LA, Chutorian AM. Pseudotumor cerebri of childhood. Am J Dis Child 1977;131:1243-8. [19]Lyons MK, Meyer FB. Cerebrospinal fluid physiology and the management of increased intracranial pressure. Mayo Clin Proc 1990;65:684-707. [20]Rubin RC, Henderson ES, Ommaya AK, Walker MD, Rall DP. The production of cerebrospinal fluid in man and its modification by acetazolamide. J Neurosurg 1966;25:430-6. [21]Maren TH, Haywood JR, Chapman SK, Zimmerman TJ. The pharmacology of methazolamide in relation to the treatment of glaucoma. Invest Ophthalmol Vis Sci 1977;16:730-42. [22]Greer M. Pseudotumor cerebri. In: Youmans JR, ed. Neurological surgery: a comprehensive reference guide to the diagnosis and management of neurosurgical problems. 2d ed. Philadelphia: Saunders, 1982:3179-95. [23]Johnston I, Besser M, Morgan MK. Cerebrospinal fluid diversion in the treatment of benign intracranial hypertension. J Neurosurg 1988;69:195-202. [24]Reinick HJ, Stein JH. Mechanism of action and clinical uses of diuretics. In: Brenner BM, Rector RC Jr, eds. The kidney. 2d ed. Philadelphia: Saunders, 1981:1097-131. [25]Vander Ark GD, Kempe LG, Smith DR. Pseudotumor cerebri treated with Lumbar-peritoneal shunt. JAMA 1971;217:1832-4. [26]Bulens C, De Vries WA, Van Crevel H. Benign intracranial hypertension. A retrospective and follow-up study. J Neurol Sci 1979;40(2-3):147-57. [27]Greer M. Benign intracranial hypertension: II. Following corticosteroid therapy. Neurology 1963;13:439-41. [28]Sorensen PS, Krogsaa B, Gjerris F. Clinical course and prognosis of pseudotumor cerebri. A prospective study of 24 patients. Acta Neurol Scand 1988;77:164-72. [29]Baker RS, Carter D, Hendrick EB, Buncic JR. Visual loss in pseudotumor cerebri of childhood. A follow-up study. Arch Ophthalmol 1985;103:1681-6. [30]Donaldson JO. Pathogenesis of pseudotumor cerebri syndromes. Neurology 1981;31:877-80. [31]Bowman MA. Pseudotumor cerebri. Am Fam Physician 1987;35(1):177-82. [32]Lessell S, Rosman NP. Permanent visual impairment in childhood pseudotumor cerebri. Arch Neurol 1986;43:801-4. CHRISTOPHER M. CODY, M.D. is an assistant clinical professor of family practice at the University of California, Davis, and has a private practice in Vallejo, Calif. Dr. Cody is a graduate of the University of California, Davis, School of Medicine. He completed a residency at the University of San Francisco Family Practice Residency, Fresno, Calif.

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