Journal of Neuro-Ophthalmology, March 2002, Volume 22, Issue 1

Clinical Features of Late-Onset Pseudotumor Cerebri Fulfilling the Modified Dandy Criteria

OBJECTIVES: To characterize the clinical features of patients with pseudotumor cerebri (PTC) fulfilling the Modified Dandy Criteria who were diagnosed at or after the age of 44 years. METHODS: We reviewed the medical records between 1987 and 1999 of 14 patients at a single institution who were diagnosed as having PTC at 44 years of age or older according to the Modified Dandy Criteria: neurologic manifestations attributable to generalized increased intracranial pressure, elevated cerebrospinal fluid pressure with normal cerebrospinal fluid composition demonstrated by lumbar puncture, and normal or small ventricles demonstrated by neuroimaging. We documented presenting symptoms and signs, significant medical conditions, and visual field follow-up. RESULTS: There were nine women and five men. Nine patients (64%) were obese. Five patients (36%) were asymptomatic. None presented with headache alone. Four patients (29%) had an identifiable cause of intracranial hypertension, including two with transverse sinus thrombosis, one with severe chronic obstructive pulmonary disease and cor pulmonale, and one with corticosteroid withdrawal after prolonged administration. During a median follow-up of 2 years of 12 patients, visual fields remained stable in 8, improved in 3, and worsened in 1. CONCLUSIONS: In comparison with patients who have idiopathic intracranial hypertension, our small series of 14 patients diagnosed after the age of 44 years were more often men, were less often obese, were less symptomatic, and had identifiable causes of intracranial hypertension in a substantial minority (29%). The visual prognosis in this age group is generally good. Because the nonidiopathic causes of PTC would be overlooked by adhering to the Modified Dandy Criteria, we propose a modification that excludes patients who have dural venous sinus disease demonstrated on magnetic resonance imaging and those who may be exposed to medications or toxins or have systemic disorders that are known to increase intracranial pressure.

ORIGINAL CONTRIBUTION Clinical Features of Late- Onset Pseudotumor Cerebri Fulfilling the Modified Dandy Criteria Sankar Bandyopadhyay, MD, and Daniel M. Jacobson, MD Objectives: To characterize the clinical features of pa­tients with pseudotumor cerebri ( PTC) fulfilling the Modi­fied Dandy Criteria who were diagnosed at or after the age of 44 years. Methods: We reviewed the medical records between 1987 and 1999 of 14 patients at a single institution who were diagnosed as having PTC at 44 years of age or older accord­ing to the Modified Dandy Criteria: neurologic manifesta­tions attributable to generalized increased intracranial pressure, elevated cerebrospinal fluid pressure with nor­mal cerebrospinal fluid composition demonstrated by lum­bar puncture, and normal or small ventricles demonstrated by neuroimaging. We documented presenting symp­toms and signs, significant medical conditions, and visual field follow- up. Results: There were nine women and five men. Nine pa­tients ( 64%) were obese. Five patients ( 36%) were asymp­tomatic. None presented with headache alone. Four patients ( 29%) had an identifiable cause of intracranial hyperten­sion, including two with transverse sinus thrombosis, one with severe chronic obstructive pulmonary disease and cor pulmonale, and one with corticosteroid withdrawal after prolonged administration. During a median follow- up of 2 years of 12 patients, visual fields remained stable in 8, im­proved in 3, and worsened in 1. Conclusions: In comparison with patients who have idio­pathic intracranial hypertension, our small series of 14 pa­tients diagnosed after the age of 44 years were more often men, were less often obese, were less symptomatic, and had identifiable causes of intracranial hypertension in a sub­stantial minority ( 29%). The visual prognosis in this age group is generally good. Because the nonidiopathic causes of PTC would be overlooked by adhering to the Modified Department of Medical Education ( SB) and Departments of Neurol­ogy and Ophthalmology ( DMJ), Marshfield Clinic, Marshfield, Wiscon­sin, USA. Address correspondence to Daniel M. Jacobson, MD, Neuro-ophthalmology ( 4F- 2), Marshfield Clinic, 1000 N. Oak Ave., Marshfield, WI 54449, USA Presented in part as a platform presentation during the Neuro-ophfhalmology session at the Annual Meeting of the American Academy of Neurology, San Diego, California, May 5, 2000. Dandy Criteria, we propose a modification that excludes patients who have dural venous sinus disease demonstrated on magnetic resonance imaging and those who may be ex­posed to medications or toxins or have systemic disorders that are known to increase intracranial pressure. ( JNeuro- Ophthalmol 2002; 22: 9- 11) Pseudotumor cerebri ( PTC) is usually diagnosed in pa­tients between the ages of 15 and 44 years. In most cases it is idiopathic, with an annual incidence of 0.9 per 100,000 persons, and 3.5 per 100,000 in women between 15 and 44 years of age ( 1). The incidence rises to 19 per 100,000 in women between 20 and 44 years of age who are 20% or more over ideal weight for their height ( 1). The Modified Dandy Criteria, as specifically expressed by Smith ( 2,3), are often used to establish the diagnosis of PTC and include the presence of symptoms and signs of increased intra­cranial pressure, no localizing neurologic signs, cerebro­spinal fluid that can show increased pressure but is analyti­cally normal, and normal to small ventricles demonstrated by neuroimaging. Although this condition has also been well character­ized in the pediatric age group ( 4- 12), we are unaware of any series exclusively reporting the clinical features of it in older patients. Therefore, the purpose of our study was to characterize the presenting clinical features, disease asso­ciations, and visual prognosis in patients with PTC fulfill­ing the Modified Dandy Criteria who were diagnosed after the age of 44 years. In so doing, we emphasize the inad­equacies of the Modified Dandy Criteria for diagnosing this condition in older patients. METHODS In reviewing the records of the Marshfield Clinic's Neuro- ophthalmology Service between the years 1987 and 1999, we identified 14 patients who had been diagnosed at 44 years of age or older as having PTC according to the Modified Dandy Criteria: neurologic manifestations attributable to generalized increased intracranial pres­sure, elevated cerebrospinal fluid pressure with normal ce­rebrospinal fluid composition demonstrated by lumbar puncture, and normal or small ventricles demonstrated by J Neuro- Ophthalmol, Vol. 22, No. 1, 2002 9 Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 Bandyopadhyay and Jacobson neuroimaging. All patients were evaluated by a single neuro- ophthalmologist ( DMJ). All patients underwent a standard neuro- ophthalmo-logic evaluation that included, in 13 patients, formal visual field assessment. One patient failed to return for testing. Another patient developed severe multifocal choroiditis shortly after diagnosis that precluded further accurate test­ing of her visual field. Visual field follow- up in the other 12 patients ranged between 6 months and 9 years ( median, 2 years). Ten patients underwent magnetic resonance imaging ( MRI), with attention to signal changes of venous sinus thrombosis. Four patients underwent computed tomogra­phy ( CT). Of the 10 patients who underwent MRI, three additionally underwent magnetic resonance venography and one additionally underwent cerebral arteriography. Of the four patients who underwent CT, one patient addition­ally underwent nuclear medicine brain scan to look for signs of venous sinus occlusion and one additionally under­went cerebral arteriography. RESULTS Nine patients ( 64%) were women and five ( 36%) were men, ranging in age from 44 to 88 years ( median age, 54 years). Nine patients ( 64%) were obese, defined by body mass index greater than 30. Five of 14 patients ( 36%) were asymptomatic, papilledema having been identified during evaluation of an unrelated problem. Visual symptoms alone led to the diagnosis in 3 of 14 patients ( 21%). One patient had visual blurring confined to one eye and was found to have ipsilateral acquired hyperopia with choroidal folds but no papilledema ( 13). One patient presented with pulsatile intracranial noises as an isolated symptom. None of the pa­tients presented with headache alone. Six of 14 patients ( 43%) reported visual loss, six ( 43%) complained of tran­sient visual obscurations, four ( 29%) had pulsatile intracra­nial noises, and one ( 7%) described double vision ( Table 2). In 4 of 13 eyes, no visual field defect was identified. In 7 of those 13 eyes, only a generalized depression was TABLE 1. Presenting symptoms in 14patients Presenting symptoms Patients, n (%) None 5 ( 36) Visual symptoms* and headache 5( 26) Visual symptoms* alone 3 ( 21) Pulsatile intracranial noises only 1 ( 7) Headache only 0 * Visual loss, transient visual obscurations, double vision TABLE 2. Presenting visual field defects in 13 patients ( 26 eyes) Visual field defect Eyes, n Generalized depression 7 Inferior nasal loss 7 Blind spot enlargement only 6 Normal 4 Superior nasal loss 1 Temporal wedge defect 1 found. In 3 patients ( 6 eyes), bilateral blind spot enlarge­ment was the only visual field abnormality identified. In the remaining 9 eyes, a focal nerve fiber bundle defect was con­sistent with optic neuropathy. No cause of intracranial hypertension was identified in 10 patients ( idiopathic intracranial hypertension). A cause was identified in the remaining four ( 29%) patients. One man had polycystic kidney disease with hypervitamin-osis A and was found to have unilateral transverse sinus thrombosis on magnetic resonance imaging and magnetic resonance venography. In one woman with an unrevealing CT scan, cerebral arteriography disclosed unilateral trans­verse sinus thrombosis. Laboratory evaluation for hyper-coagulopathy or prothrombotic conditions was unreveal­ing. One man had end- stage chronic obstructive pulmonary disease with cor pulmonale, polycythemia, and severe hypoxemia and hypercarbia. One woman was found to have papilledema as she was followed during late cortico­steroid withdrawal after chronic use for remote temporal arteritis. She had no signs of active vasculitis or ischemic optic neuropathy. Six patients did not require any treatment because they were either asymptomatic or mildly symptomatic and without significant visual field loss. Seven patients were treated with acetazolamide and one with furosemide be­cause of acetazolamide intolerance. Four patients experi­enced side effects from acetazolamide. In three of these pa­tients, acetazolamide was discontinued because of these side effects. During subsequent evaluation of the 12 patients who could be followed with formal perimetry ( median follow-up, 2 years), the visual field of eight patients, including the three with blind spot enlargement only, remained stable. The visual field defects improved in three patients and worsened in only one patient. DISCUSSION In comparison with patients with idiopathic intra­cranial hypertension, our older patients, diagnosed based on the Modified Dandy Criteria, consisted of a higher 10 © 2002 Lippincott Williams & Wilkins Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. CLINICAL FEATURES OF LATE- ONSET PSEUDOTUMOR CEREBRI JNeuro- Ophthalmol, Vol. 22, No. 1, 2002 TABLE 3. Proposed modification of the " Modified Dandy Criteria" for pseudotumor cerebri in older patients 1. Symptoms and signs limited to those attributable to elevated intracranial pressure. 2. Elevated intracranial pressure, typically assessed during lumbar puncture, with otherwise normal cerebrospinal fluid constituents. 3. No structural or vascular abnormality associated with intracranial hypertension identified during magnetic resonance imaging and magnetic resonance venography. 4. No other identifiable cause of intracranial hypertension, such as medication, toxin, or systemic disorders associated with elevated right heart pressure. proportion of men, were less frequently obese, were gener­ally less symptomatic, and more often had identifiable ( nonidiopathic) causes of PTC ( 1,14,15). None of our pa­tients presented with headache alone, unlike younger pa­tients, in whom headache is the most common symptom ( 3). Five patients had no symptoms and their papilledema was discovered during evaluation for unrelated problems. The visual prognosis, based on serial visual field examination, appeared to be good. Even though this was a retrospective analysis, we do not believe that the reported frequency of symptoms under­estimates their true occurrence, since the results of patient responses of all of the targeted symptoms were present in each medical record. Still, we recommend a prospective study, ideally using a case- control design, to confirm our observations. The use of pooled data may facilitate acqui­sition of clinical information in a timely manner. One further potential limitation of our retrospective analysis was that not all patients underwent a standardized neuroimaging and medical evaluation to seek other causes of intracranial hypertension. For example, thrombosis of a cerebral venous sinus was identified in 2 of 14 patients ( 14%). We advocate using MRI and magnetic resonance venography as the preferred method of imaging older pa­tients with suspected intracranial hypertension. The relatively high proportion of nonidiopathic causes of PTC in this series calls into question the appro­priateness of the Modified Dandy Criteria for clinical or research application in this age group of patients [ 2]. These criteria do not specify which neuroimaging procedure to use and do not specifically indicate the necessity of exclud­ing other causes of intracranial hypertension. 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