Journal of Neuro-Ophthalmology, December 1996, Volume 16, Issue 4

Normal Pressure Pseudotumor Cerebri

We present a case report of a patient with clinical features suggestive of pseudotumor cerebri (PTC), without a documented elevated measurement of intracranial pressure (ICP). Chart review was done of one patient's clinical course over a 28-month period. The patient was treated for PTC even though she never had a documented elevated ICP. Her signs and symptoms, including headache, disc edema, and visual field loss, all showed improvement with standard PTC therapy, which ultimately included optic nerve sheath fenestration (ONSF). Her presenting symptoms of clinical depression were also relieved with this treatment. PTC may present without an elevated ICP as defined by current standards. Some patients may be more susceptible to lower levels of ICP and develop this syndrome, and it may be responsive to standard PTC therapy. Further investigation may warrant that clinical depression be included as another minor symptom of PTC.

Journal of Neuro- Ophthalmology 16( 4): 241- 246, 1996. 1996 Lippincott- Raven Publishers, Philadelphia " Normal Pressure" Pseudotumor Cerebri Jeffrey P. Green, M. D., Nancy J. Newman, M. D., Zachary N. Stowe, M. D., and Charles B. Nemeroff, M. D., Ph. D. We present a case report of a patient with clinical fea­tures suggestive of pseudotumor cerebri ( PTC), without a documented elevated measurement of intracranial pressure ( ICP). Chart review was done of one patient's clinical course over a 28- month period. The patient was treated for PTC even though she never had a docu­mented elevated ICP. Her signs and symptoms, includ­ing headache, disc edema, and visual field loss, all showed improvement with standard PTC therapy, which ultimately included optic nerve sheath fenestra­tion ( ONSF). Her presenting symptoms of clinical de­pression were also relieved with this treatment. PTC may present without an elevated ICP as defined by cur­rent standards. Some patients may be more susceptible to lower levels of ICP and develop this syndrome, and it may be responsive to standard PTC therapy. Further investigation may warrant that clinical depression be in­cluded as another minor symptom of PTC. Key Words: Pseudotumor cerebri- Optic nerve sheath fenestration- Depression- Intracranial pressure. Pseudotumor cerebri ( PTC) is a syndrome of raised intracranial pressure of unknown etiology. The modified Dandy criteria for the diagnosis of PTC are well known: ( a) signs and symptoms of increased intracranial pressure; ( b) absence of lo­calized findings on neurologic examination; ( c) normal neuroradiologic studies; ( d) awake and alert patient; ( e) no other cause of increased intra­cranial pressure present ( 1). The major symptoms of PTC include headache, transient visual obscu­rations, blurred vision, pulsatile tinnitus, and dip­lopia ( 1,2). Other minor symptoms include paras-thesias, back and leg pain, arthralgias, and un­steady gait ( 3). Johnston et al. ( 4) called attention to some cases that bear a close resemblance to PTC but fail to comply with one or more of the accepted diagnos­tic criteria. These authors proposed that the con­cept of PTC be broadened to include other atypical forms. One of these atypical forms was that of so-called " normal pressure pseudotumor" syndrome. We report a patient who presented with symptoms of clinical depression and headache and possible " normal pressure pseudotumor cerebri." Her symptoms and signs improved after optic nerve sheath fenestration. Manuscript received February 23, 1996; accepted April 21, 1996. From the department of Ophthalmology ( J. P. G., N. J. N.), Neurology ( N. J. N.), Neurosurgery ( N. J. N.), Psychiatry and Be­havioral Sciences ( Z. N. S., C. B. N.), and Gynecology and Ob­stetrics ( Z. N. S.), Emory University, Atlanta, Georgia, U. S. A. This work was supported in part by a departmental grant from Research to Prevent Blindness Inc. Address correspondence and reprint requests to Dr. Nancy J. Newman, Emory Eye Center, Neuro- Ophthalmology Unit, 1327 Clifton Road NE, Atlanta, GA 30322, U. S. A. CASE REPORT An 18- year- old, 66- inch tall, 145- pound woman with a mildly overweight body habitus, was ad­mitted to the general psychiatric and clinical re­search unit with a history of depression for 15 months and chronic fatigue syndrome for approx­imately 3 years diagnosed by a local psychiatrist. Her symptoms included complaints of sadness, lack of motivation, hypersomnolence ( up to 16 h per day), hyperphagia, fatigue, difficulty concen­trating, and a history of morbid thoughts. She had b e e n t r e a t e d for 10 m o n t h s with fluoxetine 241 242 /. P. GREEN £ T AL. ( Prozac) up to 60 mg/ day, with only a partial re­mission of symptoms. The fluoxetine was discon­tinued and the patient was started on desipramine ( Norpramin) up to 100 mg/ day, which was discon­tinued secondary to a rash. Upon admission her medications included lorazepam ( Ativan) 1 mg at bedtime, and an oral contraceptive, Ortho Novum 1/ 35. Her admission Beck Depression Inventory ( BDI) ( 5) was 15, and she was started on sertraline ( Zoloft) 50 mg/ day. On her admission physical ex­amination the psychiatrist noted that she had bi­lateral disc edema. Further questioning revealed that the patient had been experiencing recurrent headaches and eye pain with no complaints of decreased visual acuity or visual field loss. She denied transient vi­sual obscurations or diplopia. She also denied the use of vitamin A, steroids, or tetracycline. On ex­amination her vision was 20/ 20 in both eyes. Pupils were normal. Intraocular pressure was 16 in both eyes, and motility and slit lamp examinations were unremarkable. Fundus examination revealed bilat­eral disc elevation ( Fig. 1), with blurred margins and mild hyperemia in both eyes. There were no spontaneous venous pulsations. Automated pe­rimetry revealed superonasal defects, right eye worse that left. ( Fig. 2). Magnetic resonance imaging with and without gadolinium was normal. A lumbar puncture re­vealed an opening pressure of 150 mm HzO, no cells, protein less than 10 mg/ dl, normal glucose, negative stains and cultures, and negative rapid plasma reagin ( RPR). Complete blood count, chemistries, pregnancy test, thyroid function tests, RPR, fluorescent trepenomal antibody ( FTA), hu­man immunodeficiency virus ( HIV), cytomegalo­virus ( CMV), and urinalysis were all negative. The antinuclear antibody ( ANA) was elevated at 1/ 320, but subsequent rheumatologic evaluation dis­closed no specific collagen vascular disorders. The day following the lumbar puncture, the pa­tient reported increased energy, decreased desire to sleep, markedly reduced headaches, and she was able to participate in group activities. Her psy­chiatrist and nursing staff noted a decrease in her depressive symptoms, specifically decreased tear­fulness, improved mood, increased energy and group attendance, and an absence of somatic com­plaints. She was discharged 7 days later with a BDI of 4. Twelve days following lumbar puncture, the patient was seen in neuro- ophthalmologic follow-up. She reported a recurrence of her headaches and psychiatric symptoms but her examination was unchanged. Fluorescein angiogram revealed bilateral disc leakage and no evidence of autofluo-rescence. Four months later the patient had continued symptoms. Her weight had not fluctuated. Her ex­amination was notable for progression of her vi­sual field defects ( Fig. 3). Repeat lumbar puncture revealed an opening pressure of 110 mm HzO, with normal CSF contents. Ten minutes after the lumbar puncture, the patient noted a decrease in her headache, and headaches did not recur until one week later. She was begun on Diamox 500 mg twice per day. One month later she reported an increase in her headaches. Her medications in­cluded Zoloft 150 mg/ day, Diamox 500 mg twice per day and Ortho Novum 1/ 35. She still reported no transient visual obscurations and no diplopia. Her neuro- ophthalmologic examination was un­changed, with the exception of further visual field loss. Her Diamox was increased to 500 mg three times per day. Five weeks later her symptoms and her visual fields were unchanged. Her weight had still not FIG. 1. Left: right eye; right: left eye. Ophthalmoscopic appearance at presentation showing disc elevation, blurred margins, and mild hyperemia. ( Green and Newman). / Neuro- Ophthalmol, Vol. 16, No. 4, 1996 PSEUDOTUMOR CEREBRI 243 FIG. 2. Visual fields at presen­tation showing superonasal de­fects, right eye greater than left. ( Green and Newman). changed. Diamox was discontinued, and she was admitted to the hospital for bolt monitoring of her intracranial pressure. Over a 48- h period, bolt monitoring revealed ICP that fluctuated between 0 and 180 mm H20. No sedation was administered while the intracranial bolt was in place. When the bolt was placed, the patient reported a decrease in headache intensity. There was no notable CSF leak around the bolt. Two days after bolt placement an optic nerve sheath fenestration was performed through a standard medial orbitotomy ( 6). There were no complications. One day postoperatively her visual acuity was unchanged, and there was no diplopia. Her intracranial pressure was moni­tored for a 24- h period postoperatively and was noted to fluctuate between 0 and 80 mm H20. One month postoperatively, the patient re­ported continued decrease in headaches since the surgery. She was still taking her Zoloft, and Ortho Novum 1/ 35, but was not on any Diamox. Her weight remained the same. Examination was no­table for improvement in her disc edema ( Fig. 4), and significant improvement in her visual fields ( Fig. 5). The patient, her family, and her psychia­trist reported a dramatic improvement in her mood with resolution of her depressive symptoms. Her Zoloft was tapered and discontinued with no re­currence of her depressive symptoms. Over the subsequent 20 months, on no medications, with­out any weight change, the patient reported one mild headache per month and has remained eu-thymic. She has returned to school and has main­tained a good sleep pattern and energy level. She has only sought medical attention for routine health care, and her neuro- ophthalmologic exam­ination has remained stable. FIG. 3. Visual fields, four months after presentation showing progression of field defects in both eyes. ( Green and Newman). / Neuro- Ophthalmol, Vol. 16, No. 4, 1996 244 /. P. GREEN ET AL. FIG. 4. Left: right eye; right: left eye. Ophthalmoscopic appearance one month postoperatively showing improve­ment of disc elevation. ( Green and Newman). DISCUSSION We believe this case represents a form of PTC with two interesting features, namely normal in­tracranial pressure and presenting symptoms of depression relieved by PTC therapy. One of the strict Dandy criteria for PTC is increased intracra­nial pressure ( 1). Corbett has said that " under no circumstances should the diagnosis of PTC be made without finding elevated spinal fluid pres­sure . . . " ( 7). Normal intracranial pressure has been defined as 136 mm H2 0 ( SD ± 37.6) in pa­tients of normal weight, and 167 mm HzO ( SD ± 36.46) in obese patients; however, it should be pointed out that there was no statistical difference between these two groups using Duncan's multi­ple range test ( 8). At no time was our patient doc­umented to have an elevated CSF pressure, includ­ing two lumbar punctures and during two days of intracranial bolt monitoring. Johnston and Pater-son ( 9) have observed wide fluctuations of CSF pressure in patients with PTC, using continuous ICP monitoring. Others have confirmed these fluc­tuations ( 10,11). The medical treatment of PTC includes weight loss, carbonic anhydrase inhibitors, and possibly systemic steroids. If these modalities are unsuc­cessful in alleviating the symptoms or curtailing the visual dysfunction caused by PTC, then surgi­cal intervention is indicated. Most authorities now agree that optic nerve sheath fenestration is the procedure of choice for progressive visual field loss and lumboperitoneal shunt the choice for intracta­ble headaches with some overlap between the two ( 12- 18). The importance of accurately diagnosing PTC is underscored by the fact that although these treatments are often highly effective, they are not without inherent side effects and complications ( 19,20). We believe that our patient represents a varia­tion of PTC that has been called " normal pressure FIG. 5. Visual fields one month postoperatively showing im­provement in field loss in both eyes. ( Green and Newman). / Neuro- Ophthalmol, Vol. 26, No. 4, 1996 PSEUDOTUMOR CEREBRI 245 PTC." Johnston et al., in a series of atypical PTC patients, reported a 13- year- old boy who was fol­lowed for four years after presenting with a uni­lateral scotoma ( 4). He had disc edema with pro­gressive visual field and acuity loss, normal neu­rologic examination, and normal CT and MRI scans of the brain. His CSF pressure was 130 mm HzO at presentation with a normal composition. One year later CSF pressure monitoring via lumber subarachnoid catheter was normal over a 36- h pe­riod. The patient's visual fields and acuity declined and, after treatment with systemic steroids was in­effective, percutaneous lumboperitoneal shunt was performed. Surgery was successful in halting visual field loss, and there was rapid resolution of disc edema. Two episodes of recurrent disc edema and worsening of visual acuity were associated with shunt obstructions, both resolving with shunt revision. This case was very similar to ours in that both patients were felt to have PTC without having a measured elevated ICP even with continuous ICP monitoring. Both patients had relief of their visual deterioration and resolution of their optic disc swelling after CSF diverting procedures. Johnston et al. proposed two possible explanations for the presence of papilledema in the absence of mea­sured elevated ICP. Firstly, it was proposed that the situation could be likened to normal- pressure hydrocephalus, in which there is a definite abnor­mality of CSF circulation and volume relieved by drainage, without a demonstrable abnormality of CSF pressure ( 4,21). Secondly, it was hypothe­sized that local abnormalities in the region of the optic nerve sheath are responsible for the develop­ment of papilledema, with relatively normal ICP allowing a local buildup of pressure that is not re­flected in the pressure measurement elsewhere in the subarachnoid space ( 4). It is possible that both these mechanisms played a role in our patient's clinical course. The former theory may have more merit than the latter, as our patient had other non-visual symptoms that resolved upon optic nerve sheath fenestration, including relief of headache, and improvement in her psychiatric symptoms. Our case supports the theory that unilateral optic nerve sheath fenestration acts as a CSF filter ( 14,22). The patient had bilateral improvement in her visual fields and bilateral resolution of her pap­illedema. This bilateral effect after unilateral sur­gery has been reported in up to 73% of cases in other series ( 15- 18). The continuous ICP monitoring also reflected a lower average ICP postoperatively. Her clinical course and response to treatment were typical of PTC. It is likely that certain patients have different susceptibilities to varying levels of ICP. On four separate occasions ( two lumbar punc­tures, subarachnoid monitor placement, and ulti­mately optic nerve sheath fenestration), our pa­tient experienced improvement in her headaches as well as her depressive symptoms. We believe that there was an undetectable amount of CSF that leaked around the subarachnoid monitor. This is a known effect that occurs with the placement of these types of monitors ( 23). If the bolt had a tight seal, we would not have expected persistent head­ache relief with its insertion. Failure to document an elevated pressure could have been due to leak­age around the subarachnoid monitor. This improvement in her headaches and depres­sive symptoms was noted subjectively by the pa­tient, and following the initial LP, by both the pa­tient and her psychiatrist. While temporally re­lated, it is unlikely that the reduction in her headaches alone accounted for her improved mood. The patient's primary complaints focused on her depressive symptoms and the headaches and eye pain were elicited only on a careful review of systems. It is reasonable to assert that the head­aches may have contributed to the clinical presen­tation and decline in function; however, the pa­tient's salutatory improvement in numerous as­pects of her life are difficult to attribute to alleviation of the subjectively mild headaches. It is possible that other confounding factors such as the placebo effect of her treatments and a desire to please her physician may have contributed to the relief of her headaches and depressive symptoms. Such confounds are equally unlikely since the pa­tient had been involved in a therapeutic relation­ship with a previous psychiatrist and had failed to respond to antidepressant treatment. In addition, the course of psychiatric treatment with an antide­pressant mechanistically very similar to previous medications, the relatively short duration of such treatment, and the maintenance of a euthymic state suggests a relationship in this patient be­tween PTC and depressive symptoms. Our patient met diagnostic criteria for major de­pression ( 24), and her symptoms were consistent with the atypical subtype of major depression. While her initial BDI score was mild to moderately severe, the BDI does not reliably assess patients with atypical symptom patterns. Furthermore, the patient demonstrated considerable social, aca­demic, and occupational impairment indicative of a major affective disorder. The majority of these symptoms were relieved transiently by lumbar punctures and persistently by optic nerve sheath fenestration. The classic symptoms and signs of / Neuro- Ophthalmol, Vol. 16, No. 4, 1996 246 /. P. GREEN ET AL. PTC include headache, transient visual obscura­tions, pulsatile intracranial noises, diplopia sec­ondary to sixth cranial nerve paresis, and papille­dema ( 1,2). Round and Keane reported on other minor symptoms of PTC, including neck stiffness, tinnitus, distal extremity parasthesias, joint pains, low back pain, and gait ataxia ( 3). Lessell ( 25), in his major review of pediatric PTC, reported that young children, excluding adolescents, may present with symptoms of irritability. He also cited the case of an infant with PTC who presented with somnolence ( 26). Other investigators have noted the association of PTC and psychiatric impairment ( 27,28). We feel that this case illustrates that clini­cal depression can be a presenting complaint of PTC and should be listed as another " minor symp­tom" of PTC. The preference of both PTC and de­pression to present in women during their child-bearing years underscores the need to investigate the relationship between these two diseases. The visual sequalae of untreated PTC can be devastating. Approximately 90% of patients with this disorder have some visual field defect, in at least one eye, and serious visual field loss or loss of visual acuity is seen in approximately 10- 25% of carefully studied patients ( 2,12,29). Diagnosis and prompt therapy may be visually preserving. We believe that a patient presenting with a clinical pic­ture indicative of PTC ( complying with the modi­fied Dandy criteria), without evidence of ICP greater than 180 mm H2 0 on at least two separate measurements, should undergo more aggressive evaluation. If clinical signs or symptoms are unre­sponsive to established tolerable medical therapy, 48- h continuous subarachnoid ICP monitoring must be considered. If the three separate ICP mea­surements including the subarachnoid monitor have all been 180 mm H2 0 or less, the diagnosis of " normal pressure pseudotumor cerebi" should be made. An accurate prevalence of this particular variant is unknown. REFERENCES 1. Wall M. Idiopathic intracranial hypertension. Neurol Clin 1991; 9( l): 73- 95. 2. Wall M, George D. Idiopathic intracranial hypertension: a prospective study of 50 patients. Brain 1991; 114: 155- 80. 3. Round R, Keane JR. The minor symptoms of increased in­tracranial pressure: 101 patients with benign intracranial hypertension. Neurology 1988; 38: 1461- 4. 4. Johnston I, Hawke S, Halmagyi M, Teo C. The pseudotu­mor syndrome: disorders of cerebrospinal fluid circulation causing intracranial hypertension without ventriculome-galy. Arch Neurol 1991; 48: 740- 7. 5. Beck AT, Steer R, Garbin M. Psychometric properties of the Beck Depression Inventory: twenty five years of evalua­tion. Clin Psychol Rev 1988; 8: 77- 100. 6. Galbraith JEK, Sullivan JH. Decompression of the perioptic meninges for relief of papilledema. Am } Ophthalmol 1973; 76: 687- 92. 7. Corbett JJ. Problems in the diagnosis and treatment of pseudotumor cerebri. Can } Neurol Sci 1983; 10: 221- 9. 8. Corbett JJ, Mehta MP. Cerebrospinal fluid pressure in nor­mal obese subjects and patients with pseudotumor cerebri. Neurology 1983; 33: 1386- 8. 9. Johnston IH, Paterson A. Benign intracranial hypertension, I: diagnosis and prognosis. Brain 1974; 97: 289- 300. 10. Gucer G, Viernstein L. Long term intracranial pressure re­cording in the management of pseudotumor cerebri. / Neu-rosurg 1978; 49: 256- 63. 11. Lyons MK, Meyer FB. Cerebrospinal fluid physiology and the management of increased intracranial pressure. Mayo Clin Proc 1990; 65: 684- 707. 12. Brourman ND, Spoor TC, Ramocki JM. Optic nerve sheath decompression for pseudotumor cerebri. Arch Ophthalmol 1988; 106: 1378- 83. 13. Radhakrishan K, Ahlskog JE, Garrity JA, Kurland LT. Id­iopathic intracranial hypertension. Mayo Clin Proc 1994; 69: 169- 80. 14. Keltner JL. Optic nerve sheath decompression. Arch Oph­thalmol 1988; 106: 1365- 9. 15. Corbett JJ, Thompson HS. The rational management of id­iopathic intracranial hypertension. Arch Neurol 1989; 46: 1049- 51. 16. Kelman SE, Sergott RC, Cioffi GA, Savino PJ, Bosley TM, Elman MJ. Modified optic nerve decompression in patients with functioning Iumboperitoneal shunts and progressive visual loss. Ophthalmology 1991; 98: 1449- 53. 17. Corbett JJ, Nerad JA, Tse DT, Anderson RL. Results of optic nerve sheath fenestration for pseudotumor cerebri. Arch Ophthalmol 1988; 106: 1391- 7. 18. Sergott RC, Savino PJ, Bosley TM. Modified optic nerve sheath decompression provides long- term visual improve­ment for pseudotumor cerebri. Arch Ophthalmol 1988; 106: 1384- 90. 19. Spoor TC, Ramocki JM, Madison MP, Wilkinson MJ. Treat­ment of pseudotumor cerebri by primary and secondary optic nerve sheath decompression. Am ] Ophthalmol 1991; 112: 177- 85. 20. Rosenberg ML, Corbett JJ, Smith C, et al. Cerebrospinal fluid diversion procedures in pseudotumor cerebri. Neurol­ogy 1993; 43: 1071- 2. 21. Adams RD, Fisher CM, Hakim S, Ojemann RG, Sweet WH. Symptomatic occult hydrocephalus with " normal" cerebro­spinal fluid pressure: a treatable syndrome. N Engl J Med 1965; 273: 117- 26. 22. Keltner JL, Albert DM, Lubow M. Optic nerve decompres­sion: a clinical pathologic study. Arch Ophthalmol 1977; 95: 97- 104. 23. Shields CB, Garretson HD, Roski R, McGraw CP: Accurate intracranial pressure monitoring. In: Ishii S, Nagai H, Brock M eds. Intracranial pressure V. Berlin: Springer- Verlag, 1983: 124- 6. 24. American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 3rd ed., revised. Washington, DC: American Psychiatric Press, 1987: 228- 33. 25. Lessell S. Pediatric pseudotumor cerebri ( idiopathic intra­cranial hypertension). Sun Ophthalmol 1992; 37: 155- 66. 26. Laverda AM, Drigo P, Casara GL. Lo pseudotumor cerebri in eta pediatrica. Minerva Pediatr 1982; 34: 961- 7. 27. Sorensen PS, Thomsen AM, Gjerris F. Persistent distur­bances of cognitive functions in patients with pseudotumor cerebri. Acta Neurol Scand 1986; 73: 264- 8. 28. Coffey CE, Ross DR, Massey EW, Olanow CW. Familial benign intracranial hypertension and depression. Can / Neurol Sci 1982; 9: 45- 7. 29. Corbett JJ, Savino PJ, Thompson S. 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. / Neuro- Ophtlmlmol, Vol. 16, No. 4, 1996