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Pseudotumor cerebri
SURVEY OF OPHTHALMOLOGY
VOLUME 23
l
NUMBER 5. MARCH-APRIL
1979
CLINICAL CHALLENGES PAUL HENKIND, EDITOR
Pseudotumor
Cerebri
JOHN L. KELTNER, M.D., NEIL R. MIUER, M.D., JOHN W. GITTINGER,M.D., AND RONALD M. BURDE,M.D. Departments of Ophthalmology, Neurology and Neurological Surgery, University of California at Davis, Sacramento, California, The Wilmer OphthalmologicalInstitute, Johns Hopkins School of Medicine, Baltimore, Maryland, Department of Ophthalmology, Tufts-New England Medical Center, Boston, Massachusetts, and Departments of Ophthalmology and Neurology, Washington University School of Medicine. St. Louis, Missouri Abstract. The authors evaluate the case of a 20-year-old, four-month-pregnant woman who presented with papilledema and visual field loss, and developed headache, intermittent diplopia and impairment of color vision over the next month. The procedures and considerations leading to the diagnosis of pseudotumor cerebri are discussed, as are the various modes of therapy and their indications. (Surv Ophthalmol 23:3 15-322, 1979)
Key words. increased intracranial pressure * lumboperitoneal * pseudotumor cerebri 1 visual field- loss papilledema
Case report: John L. Keltner, M.D., Department of Ophthalmology, University of California at Davis, Sacramento, California.
A
20-year-old, four-month-pregnant, white woman presented to our Neuro-Ophthalmology Service with papilledema and visual loss. In early January of 1978, the patient complained of loss of her nasal field in her right eye and noticed intermittent fleeting losses of vision lasting for seconds in her left eye. By early February of 1978, she complained of intermittent headaches. These headaches were occipital and temporal. She went to a chiropractor and had manipulations per315
shunt
-
formed on her neck 1 or 2 times a day for several weeks. The patient also complained of diplopia, which was worse at distance than at near. The diplopia was intermittent, and she could not relate it to any particular precipitative events. The patient’s past medical history and family history were unremarkable, and she was on no medication. General physical and neurological examination revealed a fourmonth-pregnant white woman who, aside from marked obesity, appeared to be in good health. Pertinent neuro-ophthalmic examination on February 21, 1978, included best corrected visual acuities of 20/100 in the right
316
Surv Ophthalmol
23 (5) March-April
KELTNER
1979
eye and 20/ lPs in’ the left eye. There was marked color loss in the right eye and normal color vision in the left eye. Kinetic visual fields (performed on a Goldmann perimeter) showed severe nasal and central field loss with only a remaining constricted temporal field in the right eye (Fig. 1). The left eye showed marked loss of the nasal field with preserved central vision (Fig. 2). The pupils were 4 mm in both eyes and reacted to light and accommodation with an afferent pupillary defect in the right eye. Examination of oculomotor function revealed 4 diopters of esophoria at distance; at near, the patient was orthophoric
ET AL
with minimal limitation of abduction in both eyes. The remainder of the oculomotor function examination (including saccades, pursuit, Bell’s phenomenon, and levator function) was within normal limits. Examination of the cranial nerves, exophthalmometry, carotid evaluation, and slitlamp examination were all normal. Dilated fundus exam revealed bilateral papilledema (Fig. 3). Skull x-rays and CT-scan were normal, and cerebrospinal fluid pressure was 460 mm H,O. There were no cells and protein was 40 mg% with a glucose of 80 mg%. Because the patient presented such advanced
FIG. 1. Right treatment
visual
field
before
FIG. 2. Left treatment
visual
field
before
CLINICAL
317
CHALLENGES
visual field loss, it was decided to proceed directly to a lumboperitoneal shunt. Following the shunt procedure, the patient had gradual resolution of her papilledema, the headaches ceased and vision improved. When last seen on May 18, 1978, she had recovered to a visual acuity of 20/30e2 on the right and 20/15 on the left. Kinetic visual fields (performed on the Goldmann perimeter) showed definite improvement in the right eye with recovery of the previous nasal field loss and expansion of the temporal field (Fig. 4). The left eye recovered the nasal field with only a remaining wedge defect present (Fig. 5). Color vision improved in the right eye. Fundus examination showed resolution of the papilledema with ensuing optic atrophy greater in the right than in the left eye (Fig. 6). Comments
Based on the preceding report, Drs. Neil R. Miller, John W. Gittinger and Ronald M. Burde were asked to diagnose and discuss the case. Comments of Neil R. Miller, M.D., The Wilmer Ophthalmological Institute. Baltimore, Maryland. The diagnosis of pseudotumor cerebri, as exemplified by this patient, is based on four criteria: 1) increased intracranial pressure as documented by lumbar puncture; 2) papilledema; 3) normal or small sized ventricles by neuroradiologic studies (CT scan, cerebral angiography or PEG); and 4) normal
cerebrospinal fluid composition.‘~” The age range in patients with pseudotumor cerebri is broad; however, the peak incidence seems to be in the third decade of life, and there is a two to one female preponderance.2*‘0*‘z~15 Presenting symptoms are generally headache and disturbances in visual acuity; however, patients may also complain of diplopia, tinnitus, or dizziness. Nausea and vomiting from increased intracranial pressure may occur. Pseudotumor cerebri can be associated with identifiable etiologic factors including middle ear disease, nonspecific infections, corticosteroid withdrawal, or the use of various medications such as Vitamin A, Tetracycline and Naladixic acid.’ An association with obesity and menstrual irregularity is common, and the development of pseudotumor cerebri during pregnancy is well known.9s’8 The etiology of the increased intracranial pressure in patients with pseudotumor cerebri remains obscure. Both diminished absorption of cerebrospinal fluid and cerebral edema have been postulated. Bercaw and Greer found a decreased rate of plasma uptake of intrathecally injected I-131 RISA in two patients, supporting a hypothesis of diminished cerebrospinal fluid absorption.’ Johnston and Paterson15 agree with this hypothesis and have suggested that the reduced CSF absorption is due to either an increase in pressure within the superior sagittal sinus, reversing the normal gradient between sinus and subarachnoid space, or to an increase in the resistance of cerebrospinal fluid flow across the arachnoid villi. However. re-
FIG. 3. Bilateral papilledema. Left: Right eye. Right: Left eye
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Surv Ophthalmol 23 (5) March-April 1979
cent studies by Raichle and co-workers”’ suggest that an abnormality in the cerebral microvasculature is responsible for an elevated cerebral blood volume, and that the intracranial hypertension in patients with pseudotumor cerebri can be explained only by tissue swelling due to an increase in total water content. Because pseudotumor cerebri is a selflimited process, generally resolving within three to nine months,z there are generally only two reasons to treat patients with this disorder: 1) severe, intractable headache, and 2) evidence of optic neuropathy. Methods of treatment include serial lumbar punctures,
KELTNER ET AL
treatment with dehydrating agents, diuretics, and/or corticosteroids, and surgical decompression or shunting procedures. No single procedure has been shown to be completely effective in this disorder, and the prevalence of permanent visual loss remains approximately 20-25%. 2*4It has been suggested that severely obese patients can be treated by reduction diet alone.” Jefferson and Clark” believe that surgical procedures are never required in the management of pseudotumor cerebri and have had excellent results using dehydrating agents such as Chlorthalidone. At the Johns Hopkins Hospital, patients are treated with a combination of serial lumbar
FIG. 4. Right visual field several months following lumboperitoneal shunt procedure
FIG. 5. Left visual field several months following lumboperitoneal shunt procedure
319
CLINICAL CHALLENGES
punctures and diuretic agents such as Lasix and Diamox. Surgical decompression procedures are generally used only when medical management has failed, and the patients are incapacitated by headache or have begun to show signs of progressive optic neuropathy. Although subtemporal decompression has been used in the past, the most common procedure in recent years has been the thecoperitoneal shunt. Shunting of cerebrospinal fluid from the lumbar to the peritoneal space results in a rapid resolution of papilledema and headache in most patients. Complications of the shunt procedure are minimal but include infection, shunt blockage and increased shunting resulting in headache and dizziness. In recent years, it has been suggested that decompression of the optic nerve by removal of a small portion of the optic nerve sheath just behind the globe may result in rapid resolution of papilledema and restoration of diminished visual acuity and field.6 Although this procedure is generally safe and simple to perform, I do not advocate its use since it is not specifically aimed at treating the underlying condition of increased pressure, and longterm results in patients who have undergone the procedure are not known. At the present time, patients at the Johns Hopkins Hospital, who do not respond to medical treatment within six months or who show signs of progressive optic neuropathy, undergo placement of an extradural sensor that monitors intracranial pressure.” On the basis of continuous intracranial pressure recordings, a decision is then made with
FK. 6.
respect to further therapy. The major difficulty in assessing surgical results in patients with pseudotumor cerebri is that generally these procedures are not used until evidence of optic neuropathy is already present. In such patients, it is impossible to know at what stage irreversible visual acuity or field loss has occurred. For this reason, a “successful” procedure may still be followed by optic atrophy with diminished visual acuity or reduced visual field. Comments of John W. Gittinger, M.D., Department of Ophthalmology, Tufts-New Ceneter, Medical Boston, England Massachusetts. The diagnosis of pseudotumor cerebri has been greatly simplified by the development of computerized tomography. When papilledema is found in the absence of neurological signs not attributable to increased intracranial pressure alone (i.e., sixth nerve palsies or visual loss), a CT scan should be performed to rule out intracranial mass or hydrocephalus. If the CT scan shows only normal or small ventricles, a lumbar puncture may then safely be performed. For the diagnosis of pseudotumor, the only acceptable cerebrospinal fluid abnormality is increased pressure; cells and protein should be normal. Because pseudotumor cerebri is associated in some cases with the empty sella syndrome, a lateral skull film should also be obtained.5 Once the diagnosis of pseudotumor cerebri is made, inquiry should be made into possible
Bilateral optic atrophy after resolution of papilledema.
Left: Right eye. Right: Left eye
320
Surv Ophthalmol
23 (5) March-April
1979
KELTNER
ET AL
causative factors. Otitis media in a child may repeated lumbar punctures; however, the expoint to a lateral sinus thrombosis. By a cellent results obtained by shunting imsimilar mechanism (venous outflow obstrucmediately may argue for this approach. tion), pseudotumor cerebri may occur after Comments of Ronald M. Burde, M.D., radical neck dissection16 or when a catheter Departments of Ophthalmology and has been used in the neck veins.22 In addition Neurology, Washington University School of to the various agents cited by Dr. Miller, lead and penicillin have also been associated with Medicine, St. Louis, Missouri. pseudotumor. The terms pseudotumor cerebri or benign The most important consideration is the intracranial hypertension should be reserved preservation of vision. Chronic papilledema for patients whose illness is characterized by due to pseudotumor in an adult will produce increased intracranial pressure in the absence significant visual loss in 510% of patients. of space occupying lesion, acute ventricular Serial visual acuities and fields are, therefore, enlargement or the sudden occlusion of a maessential in the management of pseudo- jor draining vein or venous sinus.2o The estumor. This complication does not seem to tablished criteria for the diagnosis include all occur in children.3 of the manifestations of increased intraTreatment usually involves some combinacranial pressure2+~20~23 (as described by Drs. Miller and Gittinger) documented by lumbar tion of repeated lumbar punctures, acetazolamide, systemic corticosteroids, and puncture.13 The presenting headache (which occurs in weight loss. Patients whose acuity is normal, more than 90% of cases1sp23) is usually whose fields show only minimal enlargement generalized in nature, worse in the morning, of the blind spots, and for whom headaches and aggravated by increasing the cerebral are not a clinical problem may need no treatment at all. When there is visual loss and venous pressure by a Valsalva maneuver maximal medical therapy has failed to con- (coughing, sneezing, etc.). Visual symptoms are always preceded by headache and occur in trol the intracranial pressure, then considerathe greater majority of patients (35-70’%~).‘~.~~ tion must be given to surgical intervention. These symptoms include transient (seconds) The two procedures which I would consider are optic nerve decompression as described by losses or blurring of vision or diplopia. Galbraith6 or a lumbo-peritoneal shunt, as Although the disease tends to run a benign, performed in Dr. Keltner’s patient. Most self-limited course, the anterior visual system is subject to the ravages of the disease. neurosurgeons prefer not to do ventriculoIn addition to the etiological factors peritoneal or ventriculo-atria1 shunts in pseudotumor patients because of the small described by Drs. Miller and Gittinger (and ventricles. Because there is greater under- excluding those processes associated with instanding of the mechanism of action and tracranial sinus thrombosis), systemic conpossibly lesser complications from shunting, I ditions such as lupus erythematosus, hypofeel this is preferable to decompression as an parathyroidism, carbon dioxide retention and plumbism have also been associated with initial procedure. One other aspect of this case deserves com- benign intracranial hypertension. The exact nature of the underlying pathoment. The patient is pregnant. The associaphysiologic mechanism is unknown. Theories tion of pseudotumor and endocrinological have been proposed invoking expansion in all disturbances is well known, and menarche of the three intracranial compartments: and pregnancy may precipitate pseudotumor. Obviously, pregnancy limits both brainstem, cerebrospinal fluid or blood. Sahs diagnostic and therapeutic options, as and JoynF’ noted an increase intracellular medications and anesthesia are risks both to and extracellular edema on light microscopy the patient and the fetus. Also, the pseudo- from tissue obtained at brain biopsy. Bercaw tumor of pregnancy appears to be limited to and Greer’ have postulated an absorption the first and second trimester, and Greer block, because they did not find labelled I-l 3 1 found that all of his cases resolved in under RISA in serum after intrathecal injection. two monthqs possibly a function of the Most recently, Raichle and co-worker? changing endocrinological environment as the have stated that intracranial hypertension can pregnancy proceeds. I would, therefore, have only be explained by tissue swelling due to inbeen tempted in this case to temporize with crease in brain-water content. In studying
321
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patients with benign intracranial hypertension, they found an abnormality of the cerebral microvasculature leading to an increase in the cerebral blood volume, but they could not define the relationship between these two parameters. Drs. Miller and Gittinger have outlined the indications for treatment and the various treatment modes that are in vogue. Obviously, no single therapeutic modality has proven to be effective. Repeated atraumatic lumbar punctures are difficult, if not impossible, in some markedly obese individuals. The use of cotticosteroids and hyperosmotic agents often aggravates an already compromised metabolic problem with the hyperosmotic agents losing their effectiveness over a short period of time. Although the use of Diamox has been discussed over the years, it is often used in homeopathic doses. Giicer and Viernstein” have shown that a dosage of 4 grams of Diamox daily is required to satisfactorily reduce intracranial pressure. Since it is known that Neptazane penetrates the blood-brain barrier more readily than Diamox, one could postulate that it would be a more effective drug in the treatment of benign intracranial hypertension. Prospective studies using both of these drugs at appropriate dosage levels are needed. Surgical intervention is only indicated when medical management has failed and the patient has demonstrated progressive visual dysfunction. Although Dr. Keltner’s patient presented with compromised central visual acuity, this is the exception rather than the rule. Since the visual loss is secondary to the changes associated with chronic papilledema the parameter that mustbe monitored is the patient’s visual field, either kinetic or static. The prevalence of permanent visual dysfunction in patients with benign intracranial hypertension remains approximately 25%.2,10 Although the lumbo- (theco-) peritoneal shunt leads to a rapid resolution of papilledema and headache, certain drawbacks exist, including technical difficulty in its performance in obese individuals and either shunt failure or excessive flow. Recently Galbraith and Sullivan,” based upon the animal work of Hayreh, demonstrated that fenestration of the optic nerve sheath was an effective method of protecting the anterior end of the optic nerve and disc from the continued effects of elevated cerebrospinal fluid pressure. This operation must be performed
each nerve individually, as the effect is postulated to be due to the collapse of the extension of the submeningeal spaces around the optic nerve, preventing compromise of the critically balanced fluid and vascular dynamics in and about the lamina cribrosa. On the other hand, the operation can be performed under local anesthesia without significant risk to the patient. on
Conclusion Benign intracranial hypertension is often not “benign” to the visual system. The obligation of the ophthalmologist is to sequentially determine the integrity of the anterior afferent visual pathways (optic nerves) by repeated visual field testing. References of intraI. Bercaw BL, Greer M: Transport thecal 131T RISA in benign intracranial Neurology (Minneap) hypertension. 20:787-790,
1970
2. Boddie
3. 4. 5.
HG, Banna M, Bradley WG: “Benign” intracranial hypertension. A survey of the clinical and radiological features, and long-term prognosis. Brain 97:313-326, 1974 Delaney P, Schellinger D: Computerized tomography and benign intracranial hypertension. JAMA 236:951-952, 1976 Foley J: Benign forms of intracranial hypertension “toxic” and “otitic hydrocephalus.” Brain 78: l-41, 1955 Foley KM, Posner JB: Does pseudotumor cerebri cause the empty sella syndrome? Neurology
(Minneap)
25:565-569,
1975
6. Galbraith 7. 8. 9.
JEK, Sullivan JH: Decompression of the perioptic meninges for relief of papilledema. Am J Ophthalmol 76:687, 1973 Glaser JS: Neuro-ophthalmology. Hagerstown, Maryland, Harper and Row, 1977 Grant WM: Toxicology of the Eye. Springfield, Charles C Thomas, 1974, ed 2 Greer M: Benign intracranial hypertension. III. Pregnancy. Neurology (Minneap) 13:670-672,
1963
IO. Greer M: Management
of benign intracranial hypertension, in Clinical Neurosurgery, Vol. 15. Baltimore, Williams and Wilkins, 1968, p 161 II. Gticer G, Viernstein L: Long-term intracranial pressure recording in the management of pseudotumor cerebri. J Neurosurg 49: 256-263,
1978
12. Guidetti
B, Guiffre R, Gambacorta D: Follow-up study of 100 cases of pseudotumor cerebri. Acta Neurochirurgica l&259-267.
1968 13. Huckman
MS,
Fox JS, Ramsey
RG, Penn
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Surv Ophtholmol 23 (5) March-April 1979
RD: Computed tomography in the diagnosis of cerebri. pseudotumor Radiology 119:593-597, 1976 14. Jefferson A, Clark J: Treatment
of benign intracranial hypertension by dehydrating agents with particular reference to the measurement of the blindspot area as a means of recording improvement. J Neurol Neurosurg Psychiat
39:627-639, 1976 15. Johnston I, Paterson
A: Benign intracranial hypertension. I. Diagnosis and prognosis; II. CSF pressure and circulation. Brain 97:289-300 and 301-312, 1974 16. Marr WG, Chambers RG: Pseudotumor cerebri syndrome following unilateral radicai neck dissection. Am J Ophthalmol51:605-611, 1961 17. Newberg B: Pseudotumor cerebri treated by rice/reduction diet. Arch Intern Med 133:802, 1974 18. Nickerson
CW, Kirk RF: Recurrent pseudotumor cerebri in pregnancy. Obstet Gynecol NY 26:811-813.
1955
KELTNER
19. Quincke
verwandte
ET AL
H: Ueber Meningitis serosa und ZustBnde. Dtsch Z Nervenheilkd
9:149-168, 1897 20. Raichle ME, Grubb
RL, Phelps ME, et al: Cerebral hemodynamics and metabolism in pseudotumor cerebri. Ann Neurol 4:104-l 11, 1978 21. Sahs AL, Joynt RJ: Brain swelling of unknown cause. Neurology (Minneap) 6:79 l-803, 1956 22. Saxena VK, Heilpern
Pseudotumor parenteral
J, Murphy SF: cerebri; a complication of hyperalimentation. JAMA
235:2124, 1976 23. Weisberg LA: Benign intracranial sion. Medicine 54:197-207, 1975
hyperten-
Reprint requests should be addressed to: Ronald M. Burde, M.D., Department of Ophthalmology, Box 8096, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63 110.
VOLUME 23
l
NUMBER 5. MARCH-APRIL
1979
CLINICAL CHALLENGES PAUL HENKIND, EDITOR
Pseudotumor
Cerebri
JOHN L. KELTNER, M.D., NEIL R. MIUER, M.D., JOHN W. GITTINGER,M.D., AND RONALD M. BURDE,M.D. Departments of Ophthalmology, Neurology and Neurological Surgery, University of California at Davis, Sacramento, California, The Wilmer OphthalmologicalInstitute, Johns Hopkins School of Medicine, Baltimore, Maryland, Department of Ophthalmology, Tufts-New England Medical Center, Boston, Massachusetts, and Departments of Ophthalmology and Neurology, Washington University School of Medicine. St. Louis, Missouri Abstract. The authors evaluate the case of a 20-year-old, four-month-pregnant woman who presented with papilledema and visual field loss, and developed headache, intermittent diplopia and impairment of color vision over the next month. The procedures and considerations leading to the diagnosis of pseudotumor cerebri are discussed, as are the various modes of therapy and their indications. (Surv Ophthalmol 23:3 15-322, 1979)
Key words. increased intracranial pressure * lumboperitoneal * pseudotumor cerebri 1 visual field- loss papilledema
Case report: John L. Keltner, M.D., Department of Ophthalmology, University of California at Davis, Sacramento, California.
A
20-year-old, four-month-pregnant, white woman presented to our Neuro-Ophthalmology Service with papilledema and visual loss. In early January of 1978, the patient complained of loss of her nasal field in her right eye and noticed intermittent fleeting losses of vision lasting for seconds in her left eye. By early February of 1978, she complained of intermittent headaches. These headaches were occipital and temporal. She went to a chiropractor and had manipulations per315
shunt
-
formed on her neck 1 or 2 times a day for several weeks. The patient also complained of diplopia, which was worse at distance than at near. The diplopia was intermittent, and she could not relate it to any particular precipitative events. The patient’s past medical history and family history were unremarkable, and she was on no medication. General physical and neurological examination revealed a fourmonth-pregnant white woman who, aside from marked obesity, appeared to be in good health. Pertinent neuro-ophthalmic examination on February 21, 1978, included best corrected visual acuities of 20/100 in the right
316
Surv Ophthalmol
23 (5) March-April
KELTNER
1979
eye and 20/ lPs in’ the left eye. There was marked color loss in the right eye and normal color vision in the left eye. Kinetic visual fields (performed on a Goldmann perimeter) showed severe nasal and central field loss with only a remaining constricted temporal field in the right eye (Fig. 1). The left eye showed marked loss of the nasal field with preserved central vision (Fig. 2). The pupils were 4 mm in both eyes and reacted to light and accommodation with an afferent pupillary defect in the right eye. Examination of oculomotor function revealed 4 diopters of esophoria at distance; at near, the patient was orthophoric
ET AL
with minimal limitation of abduction in both eyes. The remainder of the oculomotor function examination (including saccades, pursuit, Bell’s phenomenon, and levator function) was within normal limits. Examination of the cranial nerves, exophthalmometry, carotid evaluation, and slitlamp examination were all normal. Dilated fundus exam revealed bilateral papilledema (Fig. 3). Skull x-rays and CT-scan were normal, and cerebrospinal fluid pressure was 460 mm H,O. There were no cells and protein was 40 mg% with a glucose of 80 mg%. Because the patient presented such advanced
FIG. 1. Right treatment
visual
field
before
FIG. 2. Left treatment
visual
field
before
CLINICAL
317
CHALLENGES
visual field loss, it was decided to proceed directly to a lumboperitoneal shunt. Following the shunt procedure, the patient had gradual resolution of her papilledema, the headaches ceased and vision improved. When last seen on May 18, 1978, she had recovered to a visual acuity of 20/30e2 on the right and 20/15 on the left. Kinetic visual fields (performed on the Goldmann perimeter) showed definite improvement in the right eye with recovery of the previous nasal field loss and expansion of the temporal field (Fig. 4). The left eye recovered the nasal field with only a remaining wedge defect present (Fig. 5). Color vision improved in the right eye. Fundus examination showed resolution of the papilledema with ensuing optic atrophy greater in the right than in the left eye (Fig. 6). Comments
Based on the preceding report, Drs. Neil R. Miller, John W. Gittinger and Ronald M. Burde were asked to diagnose and discuss the case. Comments of Neil R. Miller, M.D., The Wilmer Ophthalmological Institute. Baltimore, Maryland. The diagnosis of pseudotumor cerebri, as exemplified by this patient, is based on four criteria: 1) increased intracranial pressure as documented by lumbar puncture; 2) papilledema; 3) normal or small sized ventricles by neuroradiologic studies (CT scan, cerebral angiography or PEG); and 4) normal
cerebrospinal fluid composition.‘~” The age range in patients with pseudotumor cerebri is broad; however, the peak incidence seems to be in the third decade of life, and there is a two to one female preponderance.2*‘0*‘z~15 Presenting symptoms are generally headache and disturbances in visual acuity; however, patients may also complain of diplopia, tinnitus, or dizziness. Nausea and vomiting from increased intracranial pressure may occur. Pseudotumor cerebri can be associated with identifiable etiologic factors including middle ear disease, nonspecific infections, corticosteroid withdrawal, or the use of various medications such as Vitamin A, Tetracycline and Naladixic acid.’ An association with obesity and menstrual irregularity is common, and the development of pseudotumor cerebri during pregnancy is well known.9s’8 The etiology of the increased intracranial pressure in patients with pseudotumor cerebri remains obscure. Both diminished absorption of cerebrospinal fluid and cerebral edema have been postulated. Bercaw and Greer found a decreased rate of plasma uptake of intrathecally injected I-131 RISA in two patients, supporting a hypothesis of diminished cerebrospinal fluid absorption.’ Johnston and Paterson15 agree with this hypothesis and have suggested that the reduced CSF absorption is due to either an increase in pressure within the superior sagittal sinus, reversing the normal gradient between sinus and subarachnoid space, or to an increase in the resistance of cerebrospinal fluid flow across the arachnoid villi. However. re-
FIG. 3. Bilateral papilledema. Left: Right eye. Right: Left eye
318
Surv Ophthalmol 23 (5) March-April 1979
cent studies by Raichle and co-workers”’ suggest that an abnormality in the cerebral microvasculature is responsible for an elevated cerebral blood volume, and that the intracranial hypertension in patients with pseudotumor cerebri can be explained only by tissue swelling due to an increase in total water content. Because pseudotumor cerebri is a selflimited process, generally resolving within three to nine months,z there are generally only two reasons to treat patients with this disorder: 1) severe, intractable headache, and 2) evidence of optic neuropathy. Methods of treatment include serial lumbar punctures,
KELTNER ET AL
treatment with dehydrating agents, diuretics, and/or corticosteroids, and surgical decompression or shunting procedures. No single procedure has been shown to be completely effective in this disorder, and the prevalence of permanent visual loss remains approximately 20-25%. 2*4It has been suggested that severely obese patients can be treated by reduction diet alone.” Jefferson and Clark” believe that surgical procedures are never required in the management of pseudotumor cerebri and have had excellent results using dehydrating agents such as Chlorthalidone. At the Johns Hopkins Hospital, patients are treated with a combination of serial lumbar
FIG. 4. Right visual field several months following lumboperitoneal shunt procedure
FIG. 5. Left visual field several months following lumboperitoneal shunt procedure
319
CLINICAL CHALLENGES
punctures and diuretic agents such as Lasix and Diamox. Surgical decompression procedures are generally used only when medical management has failed, and the patients are incapacitated by headache or have begun to show signs of progressive optic neuropathy. Although subtemporal decompression has been used in the past, the most common procedure in recent years has been the thecoperitoneal shunt. Shunting of cerebrospinal fluid from the lumbar to the peritoneal space results in a rapid resolution of papilledema and headache in most patients. Complications of the shunt procedure are minimal but include infection, shunt blockage and increased shunting resulting in headache and dizziness. In recent years, it has been suggested that decompression of the optic nerve by removal of a small portion of the optic nerve sheath just behind the globe may result in rapid resolution of papilledema and restoration of diminished visual acuity and field.6 Although this procedure is generally safe and simple to perform, I do not advocate its use since it is not specifically aimed at treating the underlying condition of increased pressure, and longterm results in patients who have undergone the procedure are not known. At the present time, patients at the Johns Hopkins Hospital, who do not respond to medical treatment within six months or who show signs of progressive optic neuropathy, undergo placement of an extradural sensor that monitors intracranial pressure.” On the basis of continuous intracranial pressure recordings, a decision is then made with
FK. 6.
respect to further therapy. The major difficulty in assessing surgical results in patients with pseudotumor cerebri is that generally these procedures are not used until evidence of optic neuropathy is already present. In such patients, it is impossible to know at what stage irreversible visual acuity or field loss has occurred. For this reason, a “successful” procedure may still be followed by optic atrophy with diminished visual acuity or reduced visual field. Comments of John W. Gittinger, M.D., Department of Ophthalmology, Tufts-New Ceneter, Medical Boston, England Massachusetts. The diagnosis of pseudotumor cerebri has been greatly simplified by the development of computerized tomography. When papilledema is found in the absence of neurological signs not attributable to increased intracranial pressure alone (i.e., sixth nerve palsies or visual loss), a CT scan should be performed to rule out intracranial mass or hydrocephalus. If the CT scan shows only normal or small ventricles, a lumbar puncture may then safely be performed. For the diagnosis of pseudotumor, the only acceptable cerebrospinal fluid abnormality is increased pressure; cells and protein should be normal. Because pseudotumor cerebri is associated in some cases with the empty sella syndrome, a lateral skull film should also be obtained.5 Once the diagnosis of pseudotumor cerebri is made, inquiry should be made into possible
Bilateral optic atrophy after resolution of papilledema.
Left: Right eye. Right: Left eye
320
Surv Ophthalmol
23 (5) March-April
1979
KELTNER
ET AL
causative factors. Otitis media in a child may repeated lumbar punctures; however, the expoint to a lateral sinus thrombosis. By a cellent results obtained by shunting imsimilar mechanism (venous outflow obstrucmediately may argue for this approach. tion), pseudotumor cerebri may occur after Comments of Ronald M. Burde, M.D., radical neck dissection16 or when a catheter Departments of Ophthalmology and has been used in the neck veins.22 In addition Neurology, Washington University School of to the various agents cited by Dr. Miller, lead and penicillin have also been associated with Medicine, St. Louis, Missouri. pseudotumor. The terms pseudotumor cerebri or benign The most important consideration is the intracranial hypertension should be reserved preservation of vision. Chronic papilledema for patients whose illness is characterized by due to pseudotumor in an adult will produce increased intracranial pressure in the absence significant visual loss in 510% of patients. of space occupying lesion, acute ventricular Serial visual acuities and fields are, therefore, enlargement or the sudden occlusion of a maessential in the management of pseudo- jor draining vein or venous sinus.2o The estumor. This complication does not seem to tablished criteria for the diagnosis include all occur in children.3 of the manifestations of increased intraTreatment usually involves some combinacranial pressure2+~20~23 (as described by Drs. Miller and Gittinger) documented by lumbar tion of repeated lumbar punctures, acetazolamide, systemic corticosteroids, and puncture.13 The presenting headache (which occurs in weight loss. Patients whose acuity is normal, more than 90% of cases1sp23) is usually whose fields show only minimal enlargement generalized in nature, worse in the morning, of the blind spots, and for whom headaches and aggravated by increasing the cerebral are not a clinical problem may need no treatment at all. When there is visual loss and venous pressure by a Valsalva maneuver maximal medical therapy has failed to con- (coughing, sneezing, etc.). Visual symptoms are always preceded by headache and occur in trol the intracranial pressure, then considerathe greater majority of patients (35-70’%~).‘~.~~ tion must be given to surgical intervention. These symptoms include transient (seconds) The two procedures which I would consider are optic nerve decompression as described by losses or blurring of vision or diplopia. Galbraith6 or a lumbo-peritoneal shunt, as Although the disease tends to run a benign, performed in Dr. Keltner’s patient. Most self-limited course, the anterior visual system is subject to the ravages of the disease. neurosurgeons prefer not to do ventriculoIn addition to the etiological factors peritoneal or ventriculo-atria1 shunts in pseudotumor patients because of the small described by Drs. Miller and Gittinger (and ventricles. Because there is greater under- excluding those processes associated with instanding of the mechanism of action and tracranial sinus thrombosis), systemic conpossibly lesser complications from shunting, I ditions such as lupus erythematosus, hypofeel this is preferable to decompression as an parathyroidism, carbon dioxide retention and plumbism have also been associated with initial procedure. One other aspect of this case deserves com- benign intracranial hypertension. The exact nature of the underlying pathoment. The patient is pregnant. The associaphysiologic mechanism is unknown. Theories tion of pseudotumor and endocrinological have been proposed invoking expansion in all disturbances is well known, and menarche of the three intracranial compartments: and pregnancy may precipitate pseudotumor. Obviously, pregnancy limits both brainstem, cerebrospinal fluid or blood. Sahs diagnostic and therapeutic options, as and JoynF’ noted an increase intracellular medications and anesthesia are risks both to and extracellular edema on light microscopy the patient and the fetus. Also, the pseudo- from tissue obtained at brain biopsy. Bercaw tumor of pregnancy appears to be limited to and Greer’ have postulated an absorption the first and second trimester, and Greer block, because they did not find labelled I-l 3 1 found that all of his cases resolved in under RISA in serum after intrathecal injection. two monthqs possibly a function of the Most recently, Raichle and co-worker? changing endocrinological environment as the have stated that intracranial hypertension can pregnancy proceeds. I would, therefore, have only be explained by tissue swelling due to inbeen tempted in this case to temporize with crease in brain-water content. In studying
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patients with benign intracranial hypertension, they found an abnormality of the cerebral microvasculature leading to an increase in the cerebral blood volume, but they could not define the relationship between these two parameters. Drs. Miller and Gittinger have outlined the indications for treatment and the various treatment modes that are in vogue. Obviously, no single therapeutic modality has proven to be effective. Repeated atraumatic lumbar punctures are difficult, if not impossible, in some markedly obese individuals. The use of cotticosteroids and hyperosmotic agents often aggravates an already compromised metabolic problem with the hyperosmotic agents losing their effectiveness over a short period of time. Although the use of Diamox has been discussed over the years, it is often used in homeopathic doses. Giicer and Viernstein” have shown that a dosage of 4 grams of Diamox daily is required to satisfactorily reduce intracranial pressure. Since it is known that Neptazane penetrates the blood-brain barrier more readily than Diamox, one could postulate that it would be a more effective drug in the treatment of benign intracranial hypertension. Prospective studies using both of these drugs at appropriate dosage levels are needed. Surgical intervention is only indicated when medical management has failed and the patient has demonstrated progressive visual dysfunction. Although Dr. Keltner’s patient presented with compromised central visual acuity, this is the exception rather than the rule. Since the visual loss is secondary to the changes associated with chronic papilledema the parameter that mustbe monitored is the patient’s visual field, either kinetic or static. The prevalence of permanent visual dysfunction in patients with benign intracranial hypertension remains approximately 25%.2,10 Although the lumbo- (theco-) peritoneal shunt leads to a rapid resolution of papilledema and headache, certain drawbacks exist, including technical difficulty in its performance in obese individuals and either shunt failure or excessive flow. Recently Galbraith and Sullivan,” based upon the animal work of Hayreh, demonstrated that fenestration of the optic nerve sheath was an effective method of protecting the anterior end of the optic nerve and disc from the continued effects of elevated cerebrospinal fluid pressure. This operation must be performed
each nerve individually, as the effect is postulated to be due to the collapse of the extension of the submeningeal spaces around the optic nerve, preventing compromise of the critically balanced fluid and vascular dynamics in and about the lamina cribrosa. On the other hand, the operation can be performed under local anesthesia without significant risk to the patient. on
Conclusion Benign intracranial hypertension is often not “benign” to the visual system. The obligation of the ophthalmologist is to sequentially determine the integrity of the anterior afferent visual pathways (optic nerves) by repeated visual field testing. References of intraI. Bercaw BL, Greer M: Transport thecal 131T RISA in benign intracranial Neurology (Minneap) hypertension. 20:787-790,
1970
2. Boddie
3. 4. 5.
HG, Banna M, Bradley WG: “Benign” intracranial hypertension. A survey of the clinical and radiological features, and long-term prognosis. Brain 97:313-326, 1974 Delaney P, Schellinger D: Computerized tomography and benign intracranial hypertension. JAMA 236:951-952, 1976 Foley J: Benign forms of intracranial hypertension “toxic” and “otitic hydrocephalus.” Brain 78: l-41, 1955 Foley KM, Posner JB: Does pseudotumor cerebri cause the empty sella syndrome? Neurology
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25:565-569,
1975
6. Galbraith 7. 8. 9.
JEK, Sullivan JH: Decompression of the perioptic meninges for relief of papilledema. Am J Ophthalmol 76:687, 1973 Glaser JS: Neuro-ophthalmology. Hagerstown, Maryland, Harper and Row, 1977 Grant WM: Toxicology of the Eye. Springfield, Charles C Thomas, 1974, ed 2 Greer M: Benign intracranial hypertension. III. Pregnancy. Neurology (Minneap) 13:670-672,
1963
IO. Greer M: Management
of benign intracranial hypertension, in Clinical Neurosurgery, Vol. 15. Baltimore, Williams and Wilkins, 1968, p 161 II. Gticer G, Viernstein L: Long-term intracranial pressure recording in the management of pseudotumor cerebri. J Neurosurg 49: 256-263,
1978
12. Guidetti
B, Guiffre R, Gambacorta D: Follow-up study of 100 cases of pseudotumor cerebri. Acta Neurochirurgica l&259-267.
1968 13. Huckman
MS,
Fox JS, Ramsey
RG, Penn
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RD: Computed tomography in the diagnosis of cerebri. pseudotumor Radiology 119:593-597, 1976 14. Jefferson A, Clark J: Treatment
of benign intracranial hypertension by dehydrating agents with particular reference to the measurement of the blindspot area as a means of recording improvement. J Neurol Neurosurg Psychiat
39:627-639, 1976 15. Johnston I, Paterson
A: Benign intracranial hypertension. I. Diagnosis and prognosis; II. CSF pressure and circulation. Brain 97:289-300 and 301-312, 1974 16. Marr WG, Chambers RG: Pseudotumor cerebri syndrome following unilateral radicai neck dissection. Am J Ophthalmol51:605-611, 1961 17. Newberg B: Pseudotumor cerebri treated by rice/reduction diet. Arch Intern Med 133:802, 1974 18. Nickerson
CW, Kirk RF: Recurrent pseudotumor cerebri in pregnancy. Obstet Gynecol NY 26:811-813.
1955
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19. Quincke
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H: Ueber Meningitis serosa und ZustBnde. Dtsch Z Nervenheilkd
9:149-168, 1897 20. Raichle ME, Grubb
RL, Phelps ME, et al: Cerebral hemodynamics and metabolism in pseudotumor cerebri. Ann Neurol 4:104-l 11, 1978 21. Sahs AL, Joynt RJ: Brain swelling of unknown cause. Neurology (Minneap) 6:79 l-803, 1956 22. Saxena VK, Heilpern
Pseudotumor parenteral
J, Murphy SF: cerebri; a complication of hyperalimentation. JAMA
235:2124, 1976 23. Weisberg LA: Benign intracranial sion. Medicine 54:197-207, 1975
hyperten-
Reprint requests should be addressed to: Ronald M. Burde, M.D., Department of Ophthalmology, Box 8096, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, Missouri 63 110.